fighting hand numbness -- surgery superior for cts november 30 … · prognostic implications of...

Fighting Hand Numbness -- Surgery Superior for CTS

Surgery Versus Non-Surgical Therapy for Carpal Tunnel Syndrome: A Randomized Parallel-Group Trial.

Jarvik JG, Comstock BA, et al:

Lancet 2009; 374 (September 26): 1074-1081

Among patients with carpal tunnel syndrome, those with a higher signal in the median nerve on MRI have poorer outcomes with surgical therapy than do those with normal to moderately abnormal median nerve signal on MRI.

Background: Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment syndrome. One previous randomized controlled trial reported greater efficacy for surgical treatment than for splinting in patients with CTS. Objective: To compare surgical versus nonsurgical treatment for CTS. Design: Multicenter, parallel-group, randomized, controlled trial. Participants: 116 subjects with CTS diagnosed clinically and electrodiagnostically. No patient had denervation on EMG. Methods: Subjects were randomly assigned to carpal tunnel surgery (n=57) or to best nonsurgical treatment (n=59), which included hand therapy, ultrasound, and splinting. Subjects underwent electrodiagnostic testing, and slightly more than 50% of subjects had MRI of the carpal tunnel. Surgery consisted of open carpal tunnel release or endoscopic decompression, as preferred by the surgeon. The primary outcome was hand function at 12 months, measured by investigators unaware of group assignment. Results: At 12 months, 101 of the 116 patients (87%) completed follow-up and were analyzed. Only 44 of the 57 patients assigned to surgery (77%) underwent surgery by 12 months, and 39% of patients assigned to nonsurgical therapy underwent surgery by 1 year. Subjects in both treatment groups improved by 3 months. During the 1-year follow-up, the improvement was significantly greater in the surgically treated group than in the group managed with nonsurgical therapy, even with intention-to-treat statistical analysis. No important adverse events and no surgical complications were reported in either group. Subjects with a distal median motor latency of <5.0 msec did as well with nonsurgical therapy as with surgical therapy. Only about 50% of subjects had wrist MRI. Subjects with normal to moderately abnormal median nerve signal on MRI were more likely to have a successful outcome with surgery than with nonsurgical care, compared to those with severely abnormal nerve signal. Conclusions: For patients with CTS without denervation, surgery modestly improves hand function and symptoms by 3 months, compared with a multimodality nonsurgical treatment regimen, and this benefit is sustained through 1 year. Reviewer's Comments: The biggest problem with this study is the number of subjects who crossed over from their assigned groups. Only 77% of the subjects assigned to surgery underwent surgery by 1 year, and 39% of subjects assigned to nonsurgical therapy underwent surgery by 1 year. However, a positive outcome with surgical therapy indicates that findings might have been even more robust in favor of surgery if subjects had not been allowed to cross over or if the data had not been analyzed by intention-to-treat analysis. (Reviewer-W. Steven Metzer, MD). © 2009, Oakstone Medical Publishing

Keywords: Carpal Tunnel Syndrome, Treatment

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Bedside HINTS Reduce Misdiagnosis in Stroke-Related AVS

HINTS to Diagnose Stroke in the Acute Vestibular Syndrome: Three-Step Bedside Oculomotor Examination More

Sensitive Than Early MRI Diffusion-Weighted Imaging.

Kattah JC, Talkad AV, et al:

Stroke 2009; 40 (November): 3504-3510

With an acute peripheral vestibulopathy, nystagmus beats in one direction only. However, with central horizontal nystagmus, the direction of the fast phase may change with direction of gaze.

Background: Neurologists are often asked to rule out a stroke in patients with acute onset of dizziness, nausea, and vomiting. An estimated 25% of such patients have a cerebral infarct, yet MRI is insensitive to small posterior fossa infarcts. Objective: To assess the sensitivity and specificity of a battery of bedside tests of vestibular-oculomotor function in an acute setting to differentiate cerebral infarction from peripheral vestibulopathy. Participants: 101 patients with acute vertigo, nausea, vomiting, and unsteady gait with or without nystagmus. Methods: Three bedside tests were evaluated for assessing head impulse, nystagmus, and test of skew (HINTS). These included (1) horizontal head impulse test (h-HIT), which tests the vestibulo-ocular reflex (usually normal in central pathology; abnormal with peripheral pathology); (2) direction-changing nystagmus (acute peripheral vestibulopathy – nystagmus beats in one direction only; central horizontal nystagmus – direction of fast phase may change with direction of gaze); and (3) skew/ocular tilt reaction. Almost all patients underwent diffusion-weighted MRI (DWI). A posterior fossa stroke was considered “confirmed” if seen on DWI. An acute peripheral vestibulopathy (APV) was considered confirmed if the clinical course was typical, was unaccompanied by neurological abnormalities, and had negative MRI findings. Most cases were confirmed by confirmatory caloric testing of vestibular function. It was hypothesized that a “benign” HINTS (abnormal h-HIT plus direction-fixed horizontal nystagmus and no skew deviation) predicted peripheral pathology. A “dangerous” HINTS battery was hypothesized to predict a posterior fossa stroke (normal h-HIT or direction-changing horizontal nystagmus, or a skew deviation). Results: Of the 101 patients evaluated, the final diagnosis was APV in 25 and central in 76 (69 ischemic strokes, 4 hemorrhages, 3 demyelinating disease/drug toxicity). In the 69 ischemic strokes, a dangerous HINTS had a 100% sensitivity and a 96% specificity for ischemic stroke. There were 5 false-negative MRIs, most commonly in the lateral medullary syndrome. With a dangerous HINTS, the positive likelihood ratio for infarct was 25.0, the negative likelihood ratio was 0. HINTS was less specific than an abnormal neurologic exam or MRI but was more sensitive to brain stem infarction. Conclusions: The 3 tests described are more sensitive than MRI for detecting posterior fossa infarcts in the first 24 to 48 hours after symptom onset. Reviewer's Comments: These simple brain stem tests are described in an appendix and in videos that are linked to the article. They are a useful addition to one's evaluation of acutely dizzy patients in an emergency setting. (Reviewer-James W. Schmidley, MD). © 2009, Oakstone Medical Publishing

Keywords: Cerebral Infarction vs Peripheral Vestibulopathy, Diagnosis


Seizures in Conjunction With PLEDs Improve Prognosis

Prognostic Implications of Periodic Epileptiform Discharges.

Orta DS, Chiappa KH, et al:

Arch Neurol 2009; 66 (August): 985-991

Stroke is the most common cause of periodic lateralized epileptiform discharges, whereas stroke and metabolic disorders are the most common causes of generalized periodic epileptiform discharges.

Objective: To determine the long-term outcome in patients with periodic epileptiform discharges (PEDs), with particular interest in determining the significance of waveform characteristics, the acute clinical situation, and neuroimaging results. Methods: Patients with the various forms of PEDs were identified from EEG data collected during a 7-year study interval. PEDs were subclassified into periodic lateralized epileptiform discharges (PLEDs), generalized periodic epileptiform discharges (GPEDs), and bilateral independent periodic lateralized discharges (BiPLEDs). The periodicity (interspike interval) and the duration and amplitude of the epileptiform complex were recorded. Morphological variables of the epileptiform discharges were also determined (polarity, total number of phases, total number of sharp waves, and distribution.) Imaging studies were classified as normal or abnormal (cortical or subcortical). Acuity was rated as acute (<4 weeks), subacute (4 to 8 weeks), chronic (>8 weeks), or acute-on-chronic. Level of functionality was classified as totally independent, partially dependent, and death. Results: 340 EEGs with PEDS were identified from 25,486 database records. Complete clinical, neurophysiological, neuroimaging, and long-term outcome data were available for 118. Stroke was the most common cause of PLEDs, whereas stroke and metabolic disorders were the most common causes of GPEDs. Forty-one patients had chronic disease, 50% with PLEDs. BiPLEDs and GPEDs were most often associated with acute or subacute disease. The prevalence of clinical seizures was 59% (70% with PLEDs, 43% with BiPLEDs, and 29.4% with GPEDs). In those with PLEDs or BiPLEDs and seizures, the etiology was most commonly stroke. Seizures in those with GPEDs were more likely of metabolic cause. At follow-up, 39% of cases were independent, 54% dependent, and 28% died. Seven patients had normal imaging. Most abnormal studies had both cortical and subcortical lesions. There was no statistical association between the history of seizures, neuroimaging, neurological findings, or functional outcome. In patients with PLEDs, logistic regression analysis showed that the occurrence of seizures was statistically less likely to be associated with death as a clinical outcome. A dependent functional outcome was more likely when PLEDs had a neoplastic rather than vascular etiology. Conclusions: In patients with PLEDs, death was associated with the absence of clinical seizures and acute etiology. A good clinical outcome was associated with a nonneoplastic etiology. Reviewer's Comments: The outcome of death and the etiology of infection, such as herpes simplex encephalitis, were not as common as might be expected. (Reviewer-John Schwankhaus, MD). © 2009, Oakstone Medical Publishing

Keywords: Periodic Epileptiform Discharges, Prognostic Indicators


Characteristic Brain MRI Lesions May Help Diagnose CJD

Updated Clinical Diagnostic Criteria for Sporadic Creutzfeldt-Jakob Disease.

Zerr I, Kallenberg K, et al:

Brain 2009; 132 (October): 2659-2668

Combining MRI abnormalities with EEG and CSF findings increases diagnostic sensitivity in Creutzfeldt-Jakob disease, with a mild drop in specificity.

Objective: To compare the sensitivity and specificity of MRI lesion patterns to EEG periodicity and CSF 14-3-3 protein detection in the diagnosis of sporadic Creutzfeldt-Jakob disease (CJD). Methods: Sporadic CJD was considered “definite” when confirmed neuropathologically and was considered “probable” on the basis of acceptable case definition criteria. Cases were subtyped by codon 129 genotyping into MM, MV, or VV. Controls consisted of patients who had been suspected of having CJD but were excluded by improvement or recovery, inflammatory CSF findings, or other diagnosis at autopsy. Iatrogenic and variant CJD cases were excluded. Sensitivity was based on the percentage of scans considered characteristic (positive) of CJD in cases. Specificity was based on the percentage of scans considered not characteristic (negative) of CJD in controls. MRI scans (fluid attenuated inversion recovery [FLAIR], diffusion-weighted imaging [DWI], or both) were performed in 436 CJD patients and 141 controls. Results: Three cortical regions (parietal, occipital, and temporal) provided the best sensitivity and specificity data, and the best diagnostic accuracy was obtained when ≥2 of these regions displayed a high signal on FLAIR, DWI, or both. For subcortical areas, optimal diagnostic accuracy correlated with high signal simultaneously in both the caudate and putamen, with DWI generally more sensitive than FLAIR. Nineteen controls had positive MRI findings. Most had infectious or inflammatory CNS disorders, including lymphocytic encephalitis, progressive multifocal leukoencephalopathy, and steroid-responsive encephalitis associated with autoimmune thyroiditis. Some had Alzheimer disease, Lewy body dementia, epilepsy, intravascular lymphomatosis, or mitochondrial cytopathy. MRI sensitivity and specificity were each 83%. For CSF14-3-3 protein detection, sensitivity was 86% but specificity was only 68%. For characteristic EEG periodicity, sensitivity was only 44%, although specificity was 92%. Conclusions: MRI should be added to EEG periodicity and CSF 14-3-3 detection as combined criteria for sporadic CJD. Currently published combined criteria have a sensitivity of 92% and a specificity of 71%. Adding characteristic MRI abnormalities would increase sensitivity to 98% of suspected cases, with specificity unchanged at 71%. Subgroup analysis suggests that these amended criteria would be especially helpful for rare subtypes such as MM2, MV1, and MV2, which can present with atypical clinical features. Reviewer's Comments: These amended criteria mean that hardly any definite cases of sporadic CJD would be missed. A specificity of 71%, however, suggests that brain biopsy would still be necessary when in vivo confirmation is needed. Inflammatory changes in the CSF will identify some cases as non-CJD, but not all. (Reviewer-John C. Brust, MD). © 2009, Oakstone Medical Publishing

Keywords: Creutzfeldt-Jakob Disease, Diagnosis


Prognosis for Comatose NCSE Depends Most on Etiology

Nonconvulsive Status Epilepticus and Coma.

Bauer G, Trinka E:

Epilepsia 2009; September 10 (): epub ahead of print

In comatose patients, outcome depends on 3 major influences: (1) structural (permanent) versus nonstructural (reversible) causes, (2) depth of coma, and (3) EEG pattern. By far the most important is the etiology.

Background: In the advanced stages of coma, patients often exhibit continuous or periodic EEG abnormalities at a time when overt seizure activity is absent. What pathophysiological role this nonconvulsive status epilepticus (NCSE) plays in perpetuating coma and aggravating brain injury is unclear. The EEG changes might reflect the late stages of irreversible brain injury and constitute an epiphenomenon, or their presence might be damaging in their own right. There is no consensus on whether treatment of NCSE in a comatose patient improves outcome, and all too often, treatment is futile. However, withholding treatment would be unethical if even a small possibility existed that NCSE per se was directly damaging. This controversial area has inconsistent terminology used to describe the variations manifested by the EEG in deepening stupor and coma. Objective: To reexamine NCSE and coma, to review the epileptiform EEG patterns and their prognostic implications, and to present a classification scheme to help guide management. Methods/Results: According to the authors, “NCSE proper” refers to a mild impairment of consciousness that is accompanied by clinical signs suggestive of status epilepticus. Examples include absence status and complex focal status epilepticus. The depth of unconsciousness never approaches coma. Patients who do reach coma and have an epileptiform EEG are called “comatose NCSE.” Importantly, comatose NCSE cannot be diagnosed without an EEG since motor signs of seizure activity are absent. These patients can be further characterized by whether their epileptiform discharges on EEG are lateralized (coma-LED) or generalized (coma-GED). This is important because the generalized patterns typically carry a worse prognosis. Between NCSE proper and comatose NCSE, there is a biological continuum that includes such disorders as subtle status epilepticus and epilepsia partialis continua on the background of severe brain injury. Outcome depends on 3 major influences: (1) structural (permanent) versus nonstructural (reversible) causes, (2) depth of coma, and (3) EEG pattern. By far the most important is the first. With certain etiologies, such as sedative overdose, the depth of coma and EEG pattern can be extreme, and yet full recovery is still the rule. With other causes of coma that produce permanent structural damage, such as hypoxia, extreme clinical and EEG patterns mean dire outcomes. Conclusions: The authors suggest that their classification scheme may help solve some of the terminologic and factual confusion surrounding NCSE. Reviewer's Comments: The authors make the case that one treats the patient and not the EEG patterns. Their classification scheme may make it easier to do so. (Reviewer-Michael Jacewicz, MD). © 2009, Oakstone Medical Publishing

Keywords: Coma, Nonconvulsive Status Epilepticus, Prognosis


BCAA Helps Make KD More Effective for Seizure Control

Branched Chain Amino Acids as Adjunctive Therapy to Ketogenic Diet in Epilepsy: Pilot Study and Hypothesis.

Evangeliou A, Spilioti M, et al:

J Child Neurol 2009; 24 (October): 1268-1272

The addition of branched chain amino acids to the ketogenic diet with a dose titrated to 20 g/day or a 2.5:1 fat-to-protein ratio may result in additional improvement in seizure control in children with epilepsy.

Background: The ketogenic diet (KD) is used for the treatment of medically refractory epilepsy in children. Approximately 50% of children treated with the KD are responders based on a ≥50% reduction in seizure frequency. Objective: To determine if the addition of branched chain amino acids (BCAA) to the KD will result in improved seizure control in children with medically refractory epilepsy. Methods: A pilot study was performed that included 17 children (age range, 2-7 years) who were treated with the KD with resultant incomplete or poor seizure control. A carbohydrate-free, powdered mixture of BCAA included 45.5 g of leucine, 30 g of isoleucine, and 24.5 g of valine. An initial dose of 5 g of this mixture was added to the daily diet. The daily dose was then increased by increments of 5 g on a weekly basis until a maximum of 20 g/day or a 2.5:1 fat-to-protein ratio was reached. Daily urine ketones and seizure records were monitored throughout the study. An EEG was obtained at baseline on the KD, and again at 1, 3, and 6 months after the addition of BCAA. Results: Approximately 50% of these children (9 of 17 patients) had achieved a ≥50% reduction in seizure frequency in response to the KD, including 1 child with a 90% reduction. In response to the addition of BCAA, 3 children became seizure-free and 5 experienced significant additional improvements. Three children who had initially achieved a 60% to 70% decrease in seizure frequency on just the KD experienced a 90% decrease in response to added BCAA. With BCAA, 1 improved from a 50% to an 80% decrease in seizure frequency, and 1 improved from a 20% to a 50% decrease. There was a tendency for further improvement in children who had responded favorably to the KD. Poor responders to KD were less likely to respond to the addition of BCAA. The addition of BCAA had no significant impact on measured urine ketones. Parents and teachers reported improvement in behavior and cognitive functions in about 50% of patients (9 of 17) following the addition of BCAA. One child improved to the point that she is now back at grade level for her age. No significant adverse effects were recognized. Discontinuation of antiepileptic medication was achieved in 1 seizure-free patient, and medication reduction was achieved in 4 others. An increase in protein content may also make the KD more tolerable. Conclusions: Approximately 50% of tested children experience significant improvement in seizure control in response to the addition of BCAA to KD. Reviewer's Comments: Although these are only pilot data, the results are promising and indicate that the addition of BCAA to the KD may improve efficacy and tolerability. Larger prospective studies are obviously warranted. (Reviewer-Gregory B. Sharp, MD). © 2009, Oakstone Medical Publishing

Keywords: Ketogenic Diet, Branched Chain Amino Acids, Improving Seizure Control


Risk Factors, Socioeconomics Strongly Impact Stroke Belt

Factors Explaining Excess Stroke Prevalence in the US Stroke Belt.

Liao Y, Greenlund KJ, et al:

Stroke 2009; 40 (October): 3336-3341

Race/ethnicity, socioeconomic factors, risk factors, and chronic diseases explain approximately 72% of the excess stroke risk that is found in the “stroke belt” in the United States.

Background: Neurologists in the United States are familiar with the concept of the “stroke belt” (SB). Less clear is why the SB has an excess stroke prevalence. Objective: To estimate how much of the excess stroke prevalence in the SB can be ascribed to race/ethnicity, socioeconomic factors, and classical stroke risk factors, such as smoking, obesity, hypertension (HTN), diabetes (DM), and coronary artery disease (CAD). Methods: The Behavioral Risk Factor Surveillance System (BRFSS), an annual health survey conducted by telephone, obtains a representative sample of each state's civilian, adult, noninstitutionalized population. Data are available from >765,000 respondents and consist of self-reported answers to questions concerning prior diagnosis of stroke, HTN, DM, or CAD. Socioeconomic questions included annual household income and amount of education. The SB was defined as Alabama, Arkansas, Georgia, Indiana, Kentucky, Louisiana, Mississippi, North Carolina, South Carolina, Tennessee, and Virginia. Approximately 150,000 respondents lived in these states. The chi square test was used to compare the population of the SB with the non-SB states. Logistic regression was used to assess the impact of state of residence on stroke risk. Results: Patients in the SB were slightly younger than elsewhere in the US. Gender distribution was equal. The SB contained more African Americans (AA), and the levels of educational attainment and income were lower in the SB. The SB states had a higher incidence of obesity than the remainder of the nation, and their populations were more likely to smoke, have HTN, DM, or CAD. The regional differences were often small, but the numbers were very large, thus differences were statistically significant and likely to be significant on a population basis. The age-standardized prevalence of self-reported stroke was higher in the SB, both among whites and AA. In the SB and elsewhere, prevalence of self-reported stroke was at least 50% higher in AA. With all covariates incorporated into the model, race/ethnicity, socioeconomic factors, risk factors, and chronic diseases explained approximately 72% of the excess risk in the SB. Conclusions: Risk factors and socioeconomic status account for most of the excess burden of stroke in the SB. Reviewer's Comments: In recent weeks, we have seen reports suggesting that billions of dollars could be saved in the United States by lowering average daily salt consumption. A provocative paper by Morganstern and colleagues suggests that the stroke risk in a Texas community is associated with proximity to fast food restaurants (Ann Neurol. 2009;66:165-170.). (Reviewer-James W. Schmidley, MD). © 2009, Oakstone Medical Publishing

Keywords: Epidemiology, Stroke Belt


Attention Declines Progressively After Radiotherapy for LGG

Cognitive and Radiological Effects of Radiotherapy in Patients With Low-Grade Glioma: Long-Term Follow-Up.

Douw L, Klein M, et al:

Lancet Neurol 2009; 8 (September): 810-818

Patients with low-grade glioma who undergo radiotherapy show long-term cognitive and radiological abnormalities. The most affected cognitive domains are attention, executive functioning, and information processing speed.

Background: In patients with low-grade glioma (LGG) studied for a mean of 6 years after diagnosis, the tumor appeared to have the most deleterious effect on cognition. Only high-fraction dose radiotherapy (>2 Gy) resulted in significant added cognitive deterioration. Objective: To assess the radiological and cognitive abnormalities in the same patient group at a mean of 12 years after the original diagnosis. Methods: Of the original 195 patients, 65 participated in this long-term follow-up study. These patients underwent neuropsychological testing (letter-digit substitution test, concept shifting tests, Stroop color-word test, visual verbal learning test, memory comparison test, and categoric word fluency). Scores were generated for 6 cognitive domains (attention, executive functioning, verbal memory, working memory, psychomotor functioning, and information processing speed). MRI scans were rated for white matter hyperintensities (WMH) and global cortical atrophy (GCA) by examiners blinded to history of radiotherapy. Results: There was a mean of 12 years between diagnosis and the second assessment. Of the 65 participants, 32 (49%) had radiotherapy at a mean of 12 years before this follow-up. Focal radiotherapy with a margin of 2 cm around the lesion was used with a mean total dose of 56.6 Gy (mean fraction dose, 1.6-2.5 Gy). The clinical variables of those receiving radiotherapy did not differ significantly from those who did not. In the first assessment at 6 years, 26 scans were rated for GCA (15 from patients who received radiotherapy) and 31 scans were rated form WMH (15 from patients who received radiotherapy). At the second assessment, 37 scans were rated for GCA (23 from patients who received radiotherapy) and 35 were rated for WMH (20 from patients who received radiotherapy). At the first assessment, there were no significant differences in cognitive performance between those with and without radiotherapy. At second assessment, patients who had radiotherapy did worse in 3 of 6 cognitive domains (attention, executive functioning, and information processing speed). Cognitive deficits were seen in 9 of those without radiotherapy (27%) and in 17 of those who had radiotherapy (53%). WMH and GCA were associated with worse cognitive function in several domains. Conclusions: Long-term LGG survivors who did not have radiotherapy showed no decline in cognition or change in MRI scans. Those with LGG who underwent radiotherapy had progressive decline in cognitive function, especially attention. Reviewer's Comments: While these results are concerning, newer radiotherapy techniques deliver less radiation to a more circumscribed area. Prospective studies are needed to evaluate these new techniques. (Reviewer-John Schwankhaus, MD). © 2009, Oakstone Medical Publishing

Keywords: Low-Grade Glioma, Radiotherapy, Cognitive Disabilities, Brain Atrophy


Rasagiline Possibly Neuroprotective in Parkinson Disease

A Double-Blind, Delayed-Start Trial of Rasagiline in Parkinson's Disease.

Olanow CW, Rascol O, et al:

N Engl J Med 2009; 361 (September 24): 1268-1278

A possible Parkinson-disease–modifying effect of early rasagiline therapy appears more robust with higher Unified Parkinson's Disease Rating Scale (UPDRS) scores, although this is not a linear measure of disease severity.

Objective: To determine if rasagiline is neuroprotective for Parkinson disease (PD). Design: Double-blind randomized trial. Participants: 1176 patients with untreated PD. The mean duration of disease was 4.5 months, and the mean total Unified Parkinson's Disease Rating Scale (UPDRS) score was 20.4. Methods: Subjects were assigned either to rasagiline (1 or 2 mg/day for 72 weeks) or to placebo for 36 weeks followed by rasagiline (1 or 2 mg/day) for 36 weeks. The latter group was the delayed-start group. To determine a positive result with either dose, the early-start treatment group had to meet 3 end points based on UPDRS scores: (1) superiority to placebo in the rate of change in the UPDRS score between weeks 12 and 36; (2) superiority to delayed-start treatment in the change in score between baseline and week 72; and (3) noninferiority to delayed-start treatment and the rate of change in UPDRS score between weeks 48 and 72. Results: 1164 subjects (99%) were included in the first primary end point analysis, and 996 subjects (85%) were included in the second and third primary end point analyses. Early-start treatment with rasagiline at 1 mg/day met all end points, with a smaller mean increase in UPDRS score between weeks 12 and 36, less worsening in the score between baseline and week 72, and noninferiority between the 2 groups with respect to rate of change in the UPDRS between weeks 48 and 72. However, all 3 end points were not met with rasagiline at 2 mg/day. Conclusions: Early treatment with rasagiline at a dose of 1 mg/day provided benefits that were consistent with a possible disease-modifying effect for PD, but early treatment with rasagiline at a dose of 2 mg/day did not. Study results must be interpreted with caution. Reviewer's Comments: The suggestion that rasagiline was neuroprotective in these PD patients is not convincing. It is difficult to explain why both doses did not provide similar results. The investigators recognize this and counseled caution in interpretation of the results. The 3 end points chosen to represent neuroprotection may not be valid, or rasagiline may not be neuroprotective. The actual changes in UPDRS scores among the groups were minimal, and it should be recognized that UPDRS scores do not represent a linear measurement of disease severity. Subjects with baseline UPDRS scores in the highest quartile who received either dose of rasagiline met all 3 primary end points. Further study is indicated. (Reviewer-W. Steven Metzer, MD). © 2009, Oakstone Medical Publishing

Keywords: Parkinson Disease, Neuroprotection, Rasagiline


Stopping Seizures -- Functional Hemispherectomy Worthwhile

Hemispherectomy: Efficacy and Analysis of Seizure Recurrence.

Limbrick DD, Narayan P, et al:

J Neurosurg Pediatr 2009; 4 (October): 323-332

Consider functional hemispherctomy in children with severe intractable epilepsy that arises from one cerebral hemisphere and contralateral hemiparesis.

Background: Hemispherectomy is sometimes performed in cases of severe refractory epilepsy that arise from one cerebral hemisphere, most commonly with an associated contralateral hemiparesis. In the mid-20th century, complete anatomic hemispherectomy was performed for this purpose and was quickly found to be associated with prominent morbidity and mortality. The technique for functional hemispherectomy was developed in the 1980s and typically included a generous resection of the inferior-lateral frontal lobe, temporal lobectomy, transventricular callosotomy, disruption of the internal capsule and corona radiata, and frontobasal disconnection. More recently, a modified periinsular hemispherectomy technique has been refined that includes corpus callosotomy and a much more limited resection of frontal and temporal opercula to permit hemispheric disconnection and selective amygdalohippocampectomy. Resultant seizure control in response to these surgeries has ranged from 40% to 90%. Objective: To evaluate the efficacy of hemispherectomy in the treatment of refractory epilepsy arising from one cerebral hemisphere and to identify potential factors that may affect outcome. Methods: A retrospective review was performed of 49 patients who underwent functional hemispherectomy. Traditional functional hemispherectomy was performed on 14 patients prior to 2003, and modified periinsular hemispherectomy was subsequently performed on 35 patients. Results: Mean duration of postsurgical follow-up was >2 years. Seizure freedom was achieved and maintained in 38 of 49 patients (78%). All 11 patients with incomplete seizure control experienced significant reduction in seizure frequency with Engel Class II outcome (rare disabling seizures) in 6 and Engel Class III outcome (worthwhile improvement) in 5. The 2 surgical techniques demonstrated no significant differences in outcome. No statistically significant factors correlated with seizure recurrence after surgery. There was a trend for bilateral abnormalities on preoperative EEG to be associated with a lesser degree of resultant seizure control. The underlying cerebral abnormality did not correlate significantly with outcome. Discontinuation of antiepileptic medication was ultimately achieved in approximately 25% of patients. Neurocognition improved in almost 90% of patients. Surgical and postsurgical complications occurred in 20% of patients, but there were no deaths or significant long-term morbidity. Reviewer's Comments: Functional hemispherectomy should be considered for children with severe intractable epilepsy that arises solely or primarily from one cerebral hemisphere, with obvious underlying structural or functional abnormality and commonly associated with contralateral hemiparesis. It is recognized that frequent seizures and prominent interictal epileptiform activity negatively impact cognitive development and function. In addition to improved seizure control, almost 90% of children in this study experienced improved neurocognitive function. (Reviewer-Gregory B. Sharp, MD). © 2009, Oakstone Medical Publishing

Keywords: Functional Hemispherectomy, Outcomes


PML Needs Early Diagnosis, Intervention

Progressive Multifocal Leukoencephalopathy After Natalizumab Monotherapy.

Linda H, von Heijne A, et al:

N Engl J Med 2009; 361 (September 10): 1081-1087

In natalizumab-induced progressive multifocal leukoencephalopathy, plasma exchange can effectively remove the drug, allowing immune reconstitution.

Objective: To describe successful treatment of progressive multifocal leukoencephalopathy (PML) in a case of multiple sclerosis (MS) treated with natalizumab. Case Report: MS was diagnosed in a 34-year-old man. Following 3 days of intravenous (IV) methylprednisolone, IV natalizumab 300 mg every 4 weeks was initiated, and his symptoms markedly improved. During 14 months of therapy, he had no clinical relapses. He then developed action-dependent myoclonus of his left arm, and MRI showed a new small MS lesion beneath the right motor cortex. Retrospective quantitative PCR analysis of saved cerebrospinal fluid (CSF) sampled before the initiation of natalizumab and at 6 and 12 months after initiation did not show Jakob-Creutzfeldt (JC) viral DNA. Natalizumab was continued, but symptoms progressed. PCR assay of CSF for JC virus was negative on 2 occasions as the MRI lesion enlarged. After 16 natalizumab infusions, PML was suspected, and plasma exchange was initiated to remove natalizumab and restore immune function. A more sensitive PCR assay identified JC virus in CSF. MRI showed further progression of the cortical lesion, and absence of contrast enhancement suggested continued viral replication. Treatment with mirtazapine was given to inhibit viral spread. Three weeks after plasma exchange, fever and headache developed, MRI showed gadolinium enhancement of the cortical lesion, and CSF showed mononuclear pleocytosis. CSF assays were now negative for JC virus DNA. Symptoms worsened, and a diagnosis of immune-reconstitution inflammatory syndrome was made. After 5 weeks of plasma exchange, fever and headache disappeared, and new MS-related cerebellar lesions were seen on MRI. CSF contained 20 mononuclear cells but no detectable JC virus DNA. MRI revealed laminar necrosis in the right motor cortex. He received IV methylprednisolone for 3 days and continued to improve. A year later after receiving interferon beta therapy, he still had left hemiparesis but no myoclonic jerking. Conclusions: A conventional PCR assay failed to identify JC virus DNA in CSF, even after symptoms attributable to PML appeared. PML lesions can be difficult to distinguish from MS lesions on MRI. Removal of natalizumab by plasma exchange led to immune-reconstitution inflammatory syndrome, in which a presumed immune attack against the JC virus increased the local brain damage. PML in patients receiving natalizumab is treatable, albeit with difficulty. Reviewer's Comments: In the same issue of the New England Journal of Medicine, two additional articles and an editorial describe aspects of PML in patients receiving natalizumab, including a report of JC viral DNA detection in CSF in the absence of attributable symptoms or MRI abnormalities. (Reviewer-John C. Brust, MD). © 2009, Oakstone Medical Publishing

Keywords: Natalizumab, Progressive Multifocal Leukoencephalopathy, Treatment


Non-Organic Neurological Diagnoses Rarely Change

Symptoms ‘Unexplained by Organic Disease’ in 1144 New Neurology Out-Patients: How Often Does the Diagnosis

Change at Follow-Up?

Stone J, Carson A, et al:

Brain 2009; 132 (October): 2878-2888

Patients with “non-organic” neurological diagnosis rarely develop an “organic” neurological disease at follow-up after 18 months.

Background: A frequently cited article by Slater (Br Med J. 1965;1:1395-1399) claims that nearly 60% of patients with an initial diagnosis of “hysteria” developed “organic” disease on follow-up. This work continues to influence modern practice, making it difficult for some neurologists to accept that some symptoms can be “non-organic.” Objective: To determine, in a large sample of neurology outpatients, the following: (1) the proportion of patients with non-organic symptoms; (2) the initial diagnosis; and (3) the proportion of patients who, during an 18-month period, develop an organic disease consistent with the presenting symptoms. Methods: Subjects were recruited prospectively into the Scottish Neurological Symptoms Study between December 2002 and February 2004, covering a population of about 5 million. The newly referred patients were rated according a 4-point scale of “completely,” “largely,” “somewhat,” and “not at all” based on whether the symptoms could be explained by an organic disease. The latter 2 categories were combined as a group with “symptoms unexplained by organic disease.” Results: Of the 3781 patients seen, 1144 patients (30%) were rated by their neurologists as having symptoms “not at all” (n=446) and “somewhat explained” (n=698) by organic disease. Of these 1144 patients, 26% had a neurological diagnosis (but with symptoms unexplained by that disease), 26% had a headache diagnosis, 18% had conversion symptoms, and 31% had another “functional” or psychological diagnosis. Follow-up information was available in 1030 of the 1144 patients (90%) via the patients' primary care physicians. The median follow-up was 19 months. Only in 4 patients did an unexpected “organic” diagnosis materialize during follow-up. The diagnostic changes consisted of multiple sclerosis (initial diagnosis: panic attacks, intermittent right-sided weakness), Alzheimer disease (initial diagnosis: anxiety), brain stem glioma (initial diagnosis: atypical facial pain), and Chiari malformation type I (initial diagnosis: migraine, possible C2 neuralgia). Eight patients had died at follow-up: 5 had an initial diagnosis of nonepileptic events. Conclusions: Among the neurological patients with initial symptoms unexplained by organic disease, a new diagnosis (which could explain the initial symptoms) rarely becomes evident to the patient's primary care physician in the 18 months following the initial neurological evaluation. Reviewer's Comments: This well-conceived study looks into the most vexing question neurologists ask themselves – am I missing an “organic” disease in this patient? The patient population appears to be quite representative of routine practice. It is quite reassuring to know that a neurologist is unlikely to miss a significant neurological problem at the initial consultation. (Reviewer-Chitharanjan Rao, MD). © 2009, Oakstone Medical Publishing

Keywords: Organic Disease, Functional, Conversion, Symptoms


Developmental Decline Seen in Children With Dravet Syndrome

Child Neurology: Dravet Syndrome: When to Suspect the Diagnosis.

Millichap JJ, Koh S, et al:

Neurology 2009; 73 (September 29): e59-62

Children with Dravet syndrome have seizure onset during the first year of life. Typically myoclonus and other seizure types develop during the second year, along with associated developmental compromise.

Objective: To describe the characteristics of Dravet syndrome (DS), previously referred to as severe myoclonic epilepsy in infancy. Results: DS is an epileptic encephalopathy with seizure onset during the first year after birth. Seizures commonly begin at about 5 to 6 months of age (range, 2-10 months). Initial seizures commonly occur with fever or illness and are often prolonged. An initial diagnosis of febrile seizures is commonly made. Seizure frequency increases during the second year, and episodes of status epilepticus are common. A prominent feature is the development of myoclonic seizures that may be generalized or focal. Other seizure types develop and often include focal and atypical absence seizures. Periods of obtundation with frequent myoclonus may occur. Fever commonly precipitates increased seizures. Seizures are not usually controlled with antiepileptic drug therapy. Mycolonus typically subsides with time, and nocturnal generalized clonic and atypical absence seizures often predominate. Early developmental progress appears normal, but signs of regression develop during the second year of life. Developmental compromise ranges from mild to fairly severe. Some children develop variable ataxia, and hyperreflexia may be apparent on examination. Prognosis is usually poor with lifelong intractable epilepsy and developmental compromise. The degree of developmental disability commonly correlates with seizure severity and frequency. The EEG is often normal at the time of seizure onset, but generalized spike wave abnormalities usually appear with time. Neuroimaging studies of the brain are normal. Differential: Severe infantile multifocal epilepsy includes focal seizures during the first year of life with later developmental decline, but epileptiform abnormalities on EEG are multifocal, and myoclonic and absence seizures are not present. Infants with benign myoclonic epilepsy have myoclonus but are developmentally normal, have a normal EEG, and have no other seizure types. Lennox-Gastaut syndrome typically includes a later onset, more tonic and atonic seizures, and slow spike and wave on EEG. Myoclonic-astatic epilepsy may be similar early on, but atonic seizures or drop attacks become prominent. DS occurs in 1 in 20,000 to 1 in 40,000 in the general population with a male to female ratio of 2:1. SCN1A mutations are identified in about 70% to 90% of patients with DS. Most mutations occur de novo but can be inherited. SCN1A mutations are present less commonly in other epileptic disorders. The SCN1A gene codes for the alpha subunit of the voltage-gated sodium channel 1.1. Reviewer's Comments: It is important to recognize the clinical features of DS. The diagnosis can be confirmed by SCN1A mutation analysis. (Reviewer-Gregory B. Sharp, MD). © 2009, Oakstone Medical Publishing

Keywords: Dravet Syndrome, Developmental Delay


Reduce NMO Relapses With Mycophenolate Mofetil

Treatment of Neuromyelitis Optica With Mycophenolate Mofetil: Retrospective Analysis of 24 Patients.

Jacob A, Matiello M, et al:

Arch Neurol 2009; 66 (September): 1128-1133

Mycophenolate mofetil (MM) may be an effective well-tolerated treatment of neuromyelitis optica (NMO) and NMO-spectrum disorders. The median annualized relapse rate was 1.28 before and 0.09 after MM treatment.

Background: Neuromyelitis optica (NMO) is an autoimmune disease of the central nervous system (CNS). Clinical disability accumulates over time in a series of relapses. Prevention of relapses is an effective strategy to minimize disability. Objective: To evaluate the efficacy and safety of mycophenolate mofetil (MM) in treating NMO. Design: Retrospective cohort study. Methods: The diagnosis of NMO was based on criteria developed by the authors (Neurology 2006;66:1485-1489). “NMO-spectrum disorders” included longitudinally extensive myelitis or optic neuritis associated with serum IgG antibodies to the astrocytic water-channel aquaporin 4 (NMO-IgG). Participants: All patients with NMO or NMO-spectrum disorders treated with MM from 1999 to 2006. Results: There were 24 patients, with a median age of 56 years (range, 34-77 years). The median duration of illness before treatment with MM was 4 years (0.1-39 years). Fifteen patients had NMO, and 9 had NMO-spectrum disorders. Seventeen patients had been treated with immunosuppressant drugs, mainly glucocorticoids and azathioprine. They were switched to MM because of continued relapses (8 patients) or medication side effects (7 patients). The median dose of MM was 2000 mg/day (range, 750-3000 mg/day). Nine patients took glucocorticoids while on MM. The median duration of treatment with MM was 2.25 years (range, 0.1-7 years), and the median duration of follow-up was 2.3 years (range, 1.5-7 years). Five patients stopped MM after a median of 1.3 years (range, 0.1-4.5 years). The median annualized relapse rate was 1.28 (range 0.23-11.78) before MM treatment and was 0.09 (range, 0-1.56) after MM treatment (P<0.001). The relapse rate improved in 19 patients (79%). The median score on the Extended Disability Status Scale (EDSS) was 6 (range, 0-8) before MM treatment and was 5.5 (range, 0-10) a median of 2.3 years later (P=0.17). The EDSS score did not change in 15 patients, improved in 7 patients, and worsened in 2. Five patients had minor side effects of MM, and 1 had leukopenia. Conclusions: MM is an effective well-tolerated treatment of NMO and NMO-spectrum disorders. The authors acknowledge several limitations of the study, including the retrospective uncontrolled design, the small sample, concomitant treatment with glucocorticoids, lack of a washout period between starting MM and stopping the preceding immunosuppressive drug, and short period of follow-up. Reviewer's Comments: Like neurosarcoidosis, NMO responds to glucocorticoids and several immunosuppressant medications, but we have no controlled trials to guide our choice of treatment. (Reviewer-Marc D. Winkelman, MD). © 2009, Oakstone Medical Publishing

Keywords: Neuromyelitis Optica, Devic Disease, Mycophenolate Mofetil


Microcephaly -- No Small Problem

Practice Parameter: Evaluation of the Child With Microcephaly (an Evidence-Based Review): Report of the Quality

Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology

Society.

Ashwal S, Michelson D, et al:

Neurology 2009; 73 (September 15): 887-897

In an infant with microcephaly, cerebral imaging should be performed when neurologic or developmental abnormalities are present or when the head circumference is 3 standard deviations below normal.

Background: Microcephaly is most commonly defined as a head circumference (HC) smaller than 2 standard deviations below the mean (<-2 SD) based on established normative data. Small head size may result from many underlying causes, and the evaluation of microcephaly is not standardized. Objective: To provide a practice parameter for the evaluation of children with microcephaly. Methods: An evidence-based review of relevant medical literature. Results: Microcephaly is diagnosed in approximately 25,000 infants and young children in the United States each year. Neuroimaging abnormalities are identified in approximately 40% of children with HC <-2 SD and in 80% of children with HC <-3 SD. MRI is more sensitive than CT in the detection of associated cerebral abnormalities, establishment of a specific diagnosis, and detection of specific malformations associated with well-described genetic conditions. Identification of a genetic abnormality or diagnosis that is responsible for microcephaly has been possible in 15% to 50% of cases. In older studies, this was primariliy based on routine karyotype analysis or clinical diagnosis of a genetic syndrome. Presently, much more extensive genetic testing is available, utilizing techniques that identify chromosome deletions, mutations, and other abnormalities resulting in a progressively increasing rate of detection of causative abnormalities. Underlying metabolic disorders have been identified as the cause of microcephaly in approximately 1% to 5% of cases. Specific metabolic testing is indicated when another explanation for microcephaly is not identified, especially when there is associated developmental compromise or regression. Genetic and metabolic testing are typically indicated when other clinical characteristics in addition to microcephaly are present and provide direction. Comorbidities commonly associated with microcephaly include mental retardation (approximately 50% of cases), epilepsy (40%), cerebral palsy (20%), and ophthalmologic disorders (20%-50%). Children with epilepsy who are microcephalic are more likely to have difficult-to-control seizures. Conclusions: Observation without neuroimaging or other testing is appropriate when small head size is proportional to weight and height and no other concerns are present. Appropriate testing should be performed as indicated when other clinical features or family history suggests a specific disease or syndrome. Cerebral imaging, preferrably with MRI, should be performed when neurologic or developmental abnormalities are present or when HC is <-3 SD. Specific genetic and metabolic testing should be performed as clinically indicated. Reviewer's Comments: This practice parameter is relatively simple and straightforward. Evaluation of microcephaly becomes more complicated when MRI does not reveal a diagnosis and other associated abnormalities are unexplained and/or progressive. (Reviewer-Gregory B. Sharp, MD). © 2009, Oakstone Medical Publishing

Keywords: Microcephaly, Evaluation


Statin Myopathy Includes Myalgias, Myositis, Rhabdomyolysis

Narrative Review: Statin-Related Myopathy.

Joy TR, Hegele RA:

Ann Intern Med 2009; 150 (June 16): 858-868

Statin-related myopathy may affect 10% of patients and can be managed by reducing the dose, nondaily dosing, or switching to another satin or bile-acid binding resin.

Background: Statins are used worldwide and are effective in reducing the prevalence of cardiovascular and cerebrovascular disease. Statin-related myopathy is an adverse effect that has resulted in a significant decrease in the use of statins in eligible patients. The precise mechanism of statin-related myopathy is not known. Proposed mechanisms include mitochondrial dysfunction or decreased cholesterol, isoprenoids, or coenzyme Q10 levels in skeletal myocytes. Objective: To review the epidemiology and management of statin-related myopathy. Methods: English-language papers were reviewed, with an emphasis on randomized controlled trials published from MEDLINE inception till October 2008. Results: There is no consensus on the definition of statin-related myopathy. Definitions may include myalgia, myopathy, myositis, and rhabdomyolysis. While randomized controlled trials reported that the incidence of statin-related myopathy is up to 5%, observational studies documented a risk as high as 10%. Rhabdomyolysis was extremely rare (1 case per 5-27 million prescriptions of statin). Predictors for statin-related myopathy include history of myopathy from another lipid-lowering agent (P<0.001), unexplained muscle cramps (P<0.001), history of creatine kinase elevation (P<0.001), family history of myopathy (P=0.022), family history of statin-related myopathy (P=0.017), and high-doses (P=0.028). Conclusions: Myopathy may affect up to 10% of patients receiving a statin, but rhabdomyolysis is rare. Risk factors include family history of statin-related myopathy, high-dose statin therapy, increased age, female gender, a history of myopathy from another lipid-lowering agent, and the use of medications metabolized through cytochrome P450 3A4. Recommended management guidelines include switching to another stain, nondaily dosing, or the use of fluvastatin, low-dose rosuvastatin, or ezetimibe. Coenzyme Q10 supplementation is not recommended for routine use. Reviewer's Comments: Neurologists are increasingly prescribing statins for patients with cerebrovascular disease and should be well aware of statin-related myopathy and its management. Merely discontinuing statins in patients with myalgia or statin-related myopathy may not be a good long-term solution, particularly for patients at high risk for stroke or myocardial infarction. This review is helpful in deciphering the myopathic adverse effects among the available statins and provides a useful approach to clinicians who prescribe statins. (Reviewer-Bashar Katirji, MD). © 2009, Oakstone Medical Publishing

Keywords: Statin-Related Myopathy


Shaky Findings -- Essential Tremor Is Risk Factor for PD

Risk of Incident Parkinson’s Disease and Parkinsonism in Essential Tremor: A Population Based Study.

Benito-Leon J, Louis ED, et al:

J Neurol Neurosurg Psychiatry 2009; 80 (April): 423-425

A patient with essential tremor (ET) is 4 to 5 times more likely to develop Parkinson disease than is someone without ET.

Objective: To assess whether patients with essential tremor (ET) are at risk for developing Parkinson disease (PD). Design: Prospective, longitudinal, population-based study. Participants: People aged ≥65 years were identified in the census of 3 communities in Spain. Methods: An evaluation was performed at baseline and 2 to 4 years later. It consisted of screening questions for ET and PD. Those with positive screens were examined, and ET and PD were diagnosed according to generally accepted criteria. A case of incident PD was defined as a subject who did not have PD at baseline but had it at follow-up. A Cox proportional hazards analysis was used to compare the risk of incident PD in people who had ET at baseline to that of people who did not (controls). Results: The 3813 participants had a mean age of 73 years and a median follow-up of 3.3 years. At baseline, 207 subjects were diagnosed with ET. None had resting tremor or other signs of PD, and there was a family history of ET in 38% of them. At follow-up, 6 of the subjects with ET (3%) and 24 of the control subjects (0.7%) had developed PD (relative risk, 4.34; P=0.001). In subjects with baseline ET, the median latency from the onset of ET to that of PD was 8 years (range, 6-13 years). Conclusions: A patient with ET is 4 to 5 times more likely to develop PD than someone without ET. A physician can use these data and published data on the lifetime risk in the general population of developing PD to advise men (8.5%) and women (5.6%) with ET of their lifetime risk of developing PD. The authors cite pathological studies that show Lewy bodies in brain stem nuclei of some patients with ET as a possible biological basis of their finding. Reviewer's Comments: For many years, clinicians have had the impression that ET is a risk factor for developing PD, but until now, there have been no reliable data to back it up. (Reviewer-Marc D. Winkelman, MD). © 2009, Oakstone Medical Publishing

Keywords: Essential Tremor, Parkinson Disease


Scans Uncover Secrets of Writer’s Cramp

Digit-Specific Aberrations in the Primary Somatosensory Cortex in Writer's Cramp.

Nelson AJ, Blake DT, Chen R:

Ann Neurol 2009; 66 (August): 146-154

Reduced inter-digit separation in the somatosensory cortex is evident on fMRI in patients with writer’s cramps.

Background: Task-specific writer's cramp (WC) is a movement disorder characterized by dystonic posturing of the hand during a specific task. Prior studies of WC have demonstrated that representations of the distances between the thumb and little finger as well as the index and little fingers are reduced in the primary somatosensory cortex. Objective: To characterize the spatial relationships, using functional magnetic resonance imaging (fMRI), among individual fingers to determine the types of aberrations that exist and whether these are specific to symptomatic fingers only. Methods: 12 right-handed patients with task-specific WC in the right hand only (7 men; mean age, 45.7 years) were recruited and compared to 12 age-matched healthy controls. The cortical representations of all fingers on the writing hand within the subregions of the postcentral gyrus were mapped in patients and controls. Vibrotactile stimuli were applied to the volar surface of each fingertip, and high-resolution 3T fMRI was done over a limited volume and included surface-based mapping techniques. Results: In area 3b, fingers directly involved in writing (thumb, index finger, and middle finger) show reduced inter-digit separation as evidenced by the reduced distance between the thumb and each finger in WC patients (P< 0.0125). The thumb representation occupied territory normally occupied by the index finger in controls. Asymptomatic ring and little fingers preserved their inter-digit separation but were shifted toward the 3 fingers directly involved in writing, consistent with reduced spacing rather than finger shifts. Area 3a was less responsive to sensory input in WC patients, providing evidence of reduced afferent drive or top-down modulation to this subregion. Conclusions: Fingers directly involved in writing (thumb, index finger and middle finger) show reduced inter-digit separation in the somatosensory cortex of patients with task-specific WC. Reviewer's Comments: This study and prior studies that included somatosensory evoked potentials indicate that abnormalities of inhibitory cortical interneurons in the sensory and motor cortex as well as the basal ganglia play an important role in WC and focal dystonias. As suggested by the authors, therapeutic regimens that help facilitate inter-digit separation of thumb, index finger, and middle finger may prove to be beneficial. (Reviewer-Bashar Katirji, MD). © 2009, Oakstone Medical Publishing

Keywords: Writer's Cramp


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