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Aug 14; 4:105. doi: 10.3389/ fneur.2013.00105. eCollection 2013.

•  This case demonstrates MMS as a sequelae of untreated neurosyphilis. •  To our knowledge, this is the first reported case of MMS associated with neurosyphilis without concomitant

immunodeficiency.

•  An etiology of cerebral vasculitis or inflammation is favored in this case given the history and presentation. •  •  Early diagnosis of MMS associated diseases could prevent the need for invasive procedures. •  •  It is important to note that his RPR continues to be positive one year after initial event and adequate treatment.

•  Centers for Disease Control and Prevention (CDC) guidelines recommend a patient with tertiary syphilis undergo screening every six months post treatment, and in some cases undergo repeat CSF evaluation, to ensure decreasing cell counts and resolution of disease.

•  On-going insidious neurosyphilis may contribute to Moyamoya collaterals which would nullify initial EDAS and place patient at risk for additional strokes.

Abstract

Figure 2. CT-Angiogram showed irregular lumen of his right ICA, A1 of right ACA, bilateral M1 segments of MCA.

Figure 4: Admission and Discharge FIM scores

Supported by an endowment from Cardinal Hill Rehabilitation Hospital and a Research Enhancement Fund from the University of Kentucky.

Discussion

Management & Outcome

Conclusions

Acknowledgements

References

Case Presentation

Moyamoya Syndrome and Cerebral Vascular Accident as a Presenting Manifestation of Neurosyphillis: A Case Report

Jamie Key, DO and Erika Erlandson, MD Department of Physical Medicine & Rehabilitation University of Kentucky, and

Cardinal Hill Rehabilitation Hospital, Lexington, KY

Case Description: A 27 year old right hand dominant Caucasian male with history of psoriasis, xanthomas, and allergic rhinitis developed acute onset left hemiparesis and slurred speech. The patient was found to have right middle and posterior cerebral arteries watershed infarcts and cerebral angiogram findings consistent with Moyamoya Disease. Additional acute care workup manifested dyslipidemia, a positive Rapid Plasma Reagin (RPR) titer, elevated Anticardiolipin IgG and IgM, as well as a positive Venereal Disease Research Laboratory (VDRL) titer suggestive of neurosyphilis. Setting: Acute Inpatient Rehabilitation Hospital Clinical Course: The patient underwent a full 14-day course of Penicillin G treatment for neurosyphilis while participating in acute rehabilitation. His Functional Independence Measures increased rapidly in comparison to other Moyamoya cases without discernable inflammatory etiology. Discussion: Historically, Moyamoya Syndrome is one of unknown etiology but has been associated with a number of diseases and illnesses including meningitis, Down syndrome, Systemic Lupus, Neurofibromatosis Type I, tuberculosis, head trauma, head irradiation, von Reckinhausen’s disease, hyperthyroidism, Tuberous Sclerosis, Marfan Syndrome, Sickle Cell Anemia, atherosclerosis, and even contraceptive use. To our knowledge, this is the first reported case of Moyamoya disease associated with neurosyphilis without concomitant immunodeficiency. In this case, a mechanism of cerebral vasculitis or inflammation is favored. On-going insidious disease may allow for further Moyamoya collaterals and impending clinical deficits and debility unless invasive measures are taken to restore cerebral circulation. Conclusions: Given an increasing number of Moyamoya cases presenting to neurorehabilitation facilities, and the likelihood of an inflammatory role in Moyamoya Syndrome, treatment of underlying illness (if available) could potentially delay or negate need for invasive revascularization procedures and promote better (and possibly quicker) outcomes in an acute rehabilitation setting. Furthermore, it might be prudent to investigate associated diseases in efforts to improve standards of care.

Acute care hospital: •  Neurosyphillis: Penicillin G, 24 million units IV daily started 10 days after symptom onset. Motor recovery did not begin

until 48 hours after treatment initiation. •  MMS: Aspirin 81mg daily for secondary stroke prevention. Definitive treatment deferred until after rehabilitation . Acute Rehabilitation: •  Admitted on day 6/14 treatment days of Penicillin G. Completed 14 day course.

•  Admission exam: Blood pressure:142/89mmHg; BMI = 35; integumentary exam revealed several psoriatic plaques with scaling on extensor surfaces of all four extremities; motor exam: 4/5 in the left lower extremity; 3/5 in proximal left upper extremity (LLE); 0/5 in distal left upper extremity (LUE); impaired sensation in LUE; and speech mildly dysarthric

27 year old right-hand-dominant Caucasian male presented with left sided weakness. Four days prior to admission had paresthesia in left hand that progressed to dense left hemiplegia, slurred speech, and a facial droop by presentation. Associated symptoms include headache, photophobia, difficulty walking, and recent insomnia.

Initial evaluation at the acute care hospital: •  National Institute of Health Stroke Scale (NIHSS) was 5. •  Diagnostic Work-Up:

•  Positive RPR titer (1:64), elevated Anticardiolipin IgG and IgM, as well as a positive VDRL •  Thyroid stimulating hormone was marginally elevated at 5.03 with a normal free T4.

•  CRP, ESR, B12, Folate, Protein S, Protein C, Factor V, and homocystine were all within normal limits. •  Cerebrospinal fluid (CSF) studies revealed elevated IgG, protein, albumin and neutrophil cell count of

48 consistent with breach of the blood brain barrier, and finally a negative culture and stain. •  Positive VDRL CSF titer of 1:2 confirming neurosyphilis.

Figure 1. MRI Head. The patient was found to have acute right middle cerebral artery (MCA) and posterior cerebral artery (PCA) watershed infarcts as well as a subacute right internal capsule (genu) infarct.

Diagnosis: Acute right MCA and PCA watershed infarcts as well as subacute right internal capsule (genu) infarct consistent with Moyamoya Syndrome (MMS). The positive VDRL CSF titer confirmed neurosyphilis.

Figure 3. Formal cerebral angiogram findings revealed severe stenosis of the right supraclinoid ICA and moderate stenosis of

the left ICA. There was also a chronic right ICA dissection.

•  Length of stay: 11 days

•  Complications: Spasticity, myoclonus, insomnia, headaches, and photophobia.

•  His Functional Independence Measures (FIM) increased rapidly in

comparison to expected course of stroke recovery Follow up: •  Repeat cerebral angiogram 2 months after onset of his original

symptoms revealed increasingly severe critical stenosis of the supraclinoid internal carotid artery with progression of pial and lenticulostriate collaterals.

•  Right encephaloduroarteriosynangiosis (EDAS) performed and he has been free of new stroke symptoms

•  Unrelated ER visit one year after symptom onset revealed

persistently positive RPR.

Moyamoya disease (MMD) vs. Moyamoya syndrome (MMS): •  Chronic occlusive cerebrovascular disorder characterized by bilateral and symmetric stenosis of the internal carotid arteries

(mainly supraclinoid portion) with compensatory enlargement of the perforating vessels at the base of the brain.

•  Collateral circulation develops around the blocked vessels which are small, friable, and prone to hemorrhage. This results in the pathognomonic “puff of smoke” appearance on cerebral angiogram.

•  In advanced disease, anterior choroidal artery, posterior communicating artery, and ophthalmic artery can become affected. The vertebro-basilar system is rarely involved.

•  Complications are dependent on area of ischemia or hemorrhage and similar to those of traditional strokes.

Etiology: •  Theories include inflammatory, genetic, infection, and autoimmune etiologies. However, despite extensive research, a clear

mechanism is still unknown. •  Cadaver studies have shown concentric and eccentric fibrocellular thickening of the intima that induces the stenosis of the

vascular lumen, and pathogenesis in the form of atherosclerosis is not appreciated.

•  CSF analysis studies recovered angiogenetic cytokines such as blast fibroblast growth factor (b-FGF), hepatocyte growth factor, and transforming growth factor (TGF). b-FGF produces the proliferation of endothelial cells which may produce the stenotic change in MMD vessels. Smooth muscle progenitor cells, CD34+ and VEGFR2+ have been described in relation to vascular remodeling.

•  Many autoimmune diseases have been reported to be related to Moyamoya phenomenon, including anti-phospholipid antibodies syndrome, systemic lupus erythematosus, Graves’ disease, and HLA class I or II alleles abnormalities.

•  RNF213 has been described as having genetic susceptibility to Moyamoya disease. Although gene function is not yet known.

•  We refer to our patients pattern as Moyamoya Syndrome (MMS) which supports a “double hit hypothesis” as the best explanation for the complex mechanism of the formation of collaterals.

 Functional Independence Measure (1-7) Items:

Rehab Admit FIMs

Rehab Discharge

FIMs

Eating 5 5 Grooming 7 7 Bathing 1 7 Upper Ext. Dressing 1 7 Lower Ext. Dressing 1 7 Toileting 4 7 Bladder 5 7 Bowel 5 7 Bed/Chair/WC transfer 4 7

Toilet transfer 4 7 Shower transfer 1 7 Walking 1 7 WC locomotion 1 7 Stair locomotion 5 6 Comprehension 5 7 Expression 6 7 Social interaction 5 7 Problem solving 4 7 Memory 4 7