w14. movement disorders for the internist dr. davide ... 12 0915 w14 martino...w14. movement...

W14. Movement Disorders for the Internist

Dr. Davide Martino, PhD MDMovement Disorders Program, DCNS, University of

Calgary

Canadian Society of Internal MedicineAnnual Meeting 2018

Banff, AB

LEARNING OBJECTIVES

1. Identify the type of tremor in patients with various presentations.

2. Determine which investigations are required in the evaluation of patients with new onset ataxic gait.

3. Manage restless legs syndrome and know which medications should not be used.

CSIM Annual Meeting 2018The following presentation represents the views of the speaker at the time of the

presentation. This information is meant for educational purposes, and should not replace

other sources of information or your medical judgment.

Conflict Disclosures “I have no conflicts to declare”

LEARNING OBJECTIVE 1

IDENTIFY THE TYPE OF TREMOR IN PATIENTS WITH VARIOUS

PRESENTATIONS

Assign to this video one of the three possible syndromic diagnoses of tremor:

A. Essential tremor B. Parkinsonian tremor C. Cerebellar tremor

Diagnosis is clinical• Topography: Tremors can occur in

any joint or muscle that is free to oscillate. Symmetry on the two sides can be important.

• Frequency: For exact frequency measurement a signal analysis of accelerometric or EMG recordings is necessary. However, with some experience the three main frequency ranges can be separated on inspection: high (>7 Hz), medium (4-7 Hz) and low (<4 Hz).

• Additional symptoms: e.g. parkinsonian syndrome, cerebellar ataxia or dystonia

…and activation• Resting tremor occurs when the muscles of the affected body part are not

voluntarily activated. Rest tremor must cease or be suppressed when a voluntary movement is initiated or performed.

• Action tremor is any tremor that is produced by voluntary contraction of muscles and covers:

• Postural tremor while voluntarily maintaining a position; • Kinetic tremor during voluntary movement.

• Simple kinetic tremor is seen during purposeless voluntary movements.

• Goal-directed tremor (most commonly labeled as intention tremor) occurs when a target is reached.

• Rarer forms of action tremor occur only during certain positions or tasks, e.g.

• task or position specific tremor• isometric tremor

Assign to this video one of the three possible syndromic diagnoses of tremor:

A. Essential tremor B. Parkinsonian tremor C. Cerebellar tremor

What is the most likely cause of this tremor?

A. Idiopathic dystonia

B. Exposure to neuroleptics (first generation antipsychotics)

C. Dystonia D. Functional movement disorder E. Lithium exposure

What is the most likely cause of this tremor?

A. Parkinson’s disease B. Hyperthyroidism C. Dystonia

D. Functional movement disorder E. Cerebellar lesion or degeneration


DETERMINE WHICH INVESTIGATIONS ARE REQUIRED IN THE EVALUATION OF

PATIENTS WITH NEW ONSET ATAXIC GAIT

?

Metronidazole-inducedacute ataxia

[Hari et al. 2013]

Acute-Subacute

Onset

Persistent

Episodic

Age at onsetViral infections: VZV (children)-

EBV (adults)

MS

SREAT

Paraneoplastic

Wernicke

Stroke

Drugs/Toxins

Genetic episodic ataxias

MS

Stroke

Drug history(CT)/MRI

Thyroid antibodies (anti-TPO + anti-Tg)

If appropriateParaneoplastic panel (anti-Hu, anti-Yo, anti-Ri, anti-CMV)

CSF

With vestibular symptoms/signs?

(nystagmus, vertigo, others)

LithiumPhenytoin

5-fluorouracilCapecitabine

Cytosine arabinosideMetronidazole

Amiodarone

Hg-Pb-MnToluene-benzene

derivativesAlcohol-malnutrition

CEREBELLAR

Look for oculomotor abnormalities

Cognitive changes –nystagmus/abducenspalsy/papilloedema

Cognitive/speech changes – tremor –

myoclonus – seizures –sleep probl - psychosis

Episodic ataxias (aut dom)Attacks precipitated by stress or emotions

EA1 (KCNA1)Delayed rectifierpotassium channel, Kv1.1

Onset: late childhoodto adolescence

Attacks: secs-mins

Interictal myokimia or neuromyotonia with stiffness and weakness duringattacks

Responds to acetazolamide

EA2 (CACNA1A)P/Q-type calcium channel alpha 1A subunit

Onset: infancy to early adulthood

Attacks: hours to days, with vertigo, nausea, ± headacheInterictal downbeat nystagmus, ataxia and rarely dystonia

Responds to acetazolamide or 4-aminopyridine

Allelic to SCA6, IGE, FHM type 1, congenital ataxia and hemiplegic migraine with cerebral edema

Acute-Subacute

Onset

Persistent

Vitamin deficiency (B12, E, folic acid)

Neurosarcoidosis

Vertebrobasilarinsufficiency

Syphilis

Drugs/Toxins

Sensory polyneuropathies

Associated with proprioceptive sensory loss de-afferentation

ataxia

CDDP, cisplatin, carboplatin, oxaliplatin

DoxorubicinBortezomib

Suramin sodiumThalliumPenicillin

Subacute combined

degeneration

• Drug history• Vitamin B12 (MMA-Hcy)

and E• MRI spine• CXR/CT chest + serum

markers of sarcoidosis (SAA, sIL-2R, ACE, KL-6)

• Syphilis serology• NCS/CSF, anti-GQ1b

Cognitive – depression - neuropathy – spastic

para/tetraparesis

Rapidprogression

Sporadic

Inherited

Age at onset

SREAT

Paraneoplastic

CJD

GSS(PRNP gene: P102L most

frequently)

MRIThyroid

antibodiesCSF/EEG

Cognitive/speech changes – tremor –

myoclonus – seizures –sleep probl - psychosis

Cognitive – psychosis and agitation -

depression

What is the most likely diet that has improved this patient’s ataxia?

A. Low-protein diet B. Ketogenic diet C. Feingold diet

D. Atkins diet E. Gluten-free diet

[Hernàndez-Lahoz et al. 2014]

66-yr old woman

4-year hx gait and

hearing problems

Forgetfulness – mood

No hx of trauma or

intradural surgery

Babinski on the right

Serum iron mildly

decreased

Serum ferritin mildly

increased

What is the most likely cause for this patient’s ataxia?

A. Folic acid deficiency B. Neuroferritinopathy

C. Superficial siderosis of the CNS D. Spontaneous intracranial hypotension

E. Vitamin E deficiency

[Bae et al. J Mov Disord 2014]

SLOW PROGRESSION ATAXIAS

Sporadic

Alcohol-related* chronic thiamine deficiency; 11-27% of chronic alcohol users

// gait and LL>UL and speech // vermal atrophy

Gluten ataxia* anti-TG6 IgA (73%) // most have cerebellar atrophy // responds

to gluten-free diet // PNpathy in 40%

Metabolic subacute combined degeneration* // vit.E, vit.B1 // hypothyroidism

and hypoparathyroidism

Toxic lithium, phenytoin, 5-FU, capecitabine, citarabine, metronidazole and

other azoles, amiodarone, heavy metals and solvents (Hg, Pb, Mn,

toluene/benzene derivatives)

Infections neurosyphilis*, Lyme*, Whipple’s

Superficial siderosis +hearing loss, pyramidal, cognitive, seizures, visual loss,

hyposmia

MSA-C and heredodegenerative ataxias


MANAGE RESTLESS LEGS SYNDROME AND KNOW WHICH MEDICATIONS

SHOULD NOT BE USED

CASE #1

34-yr old nurse referred for early insomnia (on bad days latency of up to 2-3 hrs),

non-refreshing sleep (frequent awakenings, 3-5 times per night, with achy legs;

partner prefers to sleep in different bed), and malaise throughout the day

Onset in late adolescence, but as a child she suffered from «growing pains» in her

legs and feeling that her legs were only loosely attached to her body and at times

hard to control

Aches and irritating discomfort in her legs during the evening, initially attributed to

stress and shiftwork – urgency to move her legs to alleviate the discomfort,

especially when lying or sitting down (typically not occurring around a daytime

nap)

Relaxation training, sleep health habits, prescription hypnotics (temazepam 30mg

hs) unsuccessful

PSG observation of PLMS, with short arousals in 70% of them

5 cups of strong coffee throughout the day

Serum ferritin = 24 ng/mL

[from sleepdisorders.sleepfoundation.orgNational Sleep Foundation]

How do we approach this patient with RLS?

Key questions

1. Have we ruled out the main causes of secondary RLS? What are these?

o Medical conditions: iron deficiency ( Ferrous sulfate + vit.C), end-stage

renal disease/on hemodialysis (vit.C + E suppl – ropinirole, L-dopa, exercise), obesity, COPD, DM, IBS

o Neurological diseases: small fibre neuropathies, PD

o Drugs: DR blockers, NSRIs, AEDs (e.g. zonisamide)

o Pregnancy

2. Is RLS sufficiently severe to warrant specific treatment?

o Strong evidence (AAN Level A) pramipexole [0.125, 0.25-0.5mg],

rotigotine patch [1, 1-3mg], gabapentin enacarbil [600, 600mg]

o Moderate evidence ropinirole [0.25, 0.25-4mg], pregabalin*, IV ferric

carboxymaltase* [500mg given twice 5 days apart]

o Weak evidence L-dopa*


Key questions

3. Should we target sleep disruption?

o PLMS [PLMI index on PSG] causing frequent awakenings: ropinirole,

pramipexole, rotigotine, pregabalin

o Improving TST, sleep efficiency, sleep latency, wake after sleep onset:

ropinirole, gabapentin enacarbil, pregabalin

o Subjective sleep measures: gabapentin enacarbil, ropinirole,

pregabalin>pramipexole, rotigotine, L-dopa

4. Risk of augmentation?

o Pregabalin / Gabapentin enacarbil

o Pramipexole / Ropinirole / Rotigotine

o L-dopa


Key questions

Is the patient not responding to treatments mentioned so far?

o Prolonged-release oxycodone/naloxone (Level C evidence for RLS symptoms,

subjective sleep symptoms, and QoL) short courses, very close monitoring!

Cannabis? Insufficient evidence

Non-pharmacologic approaches?

o Pneumatic compression (inflatable garments and electrical pneumatic pump)

before usual symptom onset likely effective

o NIBS near-infrared stimulation and rTMS (SMA,M1) possibly effective

o tDCS probably ineffective

o Vibrating pads possibly ineffective

o Acupuncture insufficient evidence

CASE #2 72-yr old lady suffering from RLS symptoms since age 30, hospitalized for severe

mood disorder and aggravation of RLS and insomnia

Ropinirole ineffective up to 5.5mg daily (recent rapid increases)

Described a «burst of heat radiating from legs to head», toes’ pain and warm

feeling in both feet, relieved by movement; sometimes restless feeling also in

upper limbs and trunk

Both sister and mother had RLS

No psychoactive substances (previous course of sertraline worsened RLS)

Comorbidities: glaucoma, spondylodegenerative changes (C-L), LLEE varicose

veins, joint pain, stress incontinence

Bloodwork ok (HGB 13.0g/dL, ferritin 100ng/ml, EGFR >60ml/min/1.73) apart from

fasting glucose 5.6 mmol/L

PLMI left leg 47.7/h, right leg 49.9/h

NCS advanced axonal neuropathy of both sural nerves (L>R)

HOW SHALL WE APPROACH THIS CASE?

[from Narowska et al., 2015]

CASE #2

1. Have we ruled out the main causes of secondary RLS?

2. Is RLS sufficiently severe to warrant specific treatment?

3. Should we target sleep disruption?

4. Risk of augmentation?

[from Narowska et al., 2015]

CASE #3

35-yr old lady diagnosed with RLS in

adolescence, very intermittent in severity

Third trimester of pregnancy: sudden

worsening of symptoms (at least 3 days a

week), circadian occurrence related to

fatigue and evening exercise

No other significant complications in

pregnancy or delivery

HOW SHALL WE APPROACH THIS

CASE?

[from Policiano et al., 2014; Garbazza & Manconi, 2018]

w14. movement disorders for the internist dr. davide ... 12 0915 w14 martino...w14. movement...

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