W14. Movement Dis isorders for r the In Internist Dr. . David - - PowerPoint PPT Presentation

• W14. Movement Dis

isorders for r the In Internist Dr. . David ide Mart rtino, PhD MD

Movement Disorders Program, DCNS, University of Calgary

Canadian Society of Internal Medicine

Annual 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 2018

The 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
• ther 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

• scillate. 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)
• ccurs 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

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

LEARNING OBJECTIVE 2

DETERMINE WHICH INVESTIGATIONS ARE REQUIRED IN THE EVALUATION OF PATIENTS WITH NEW ONSET ATAXIC GAIT

?

?

Metronidazole-induced acute ataxia

[Hari et al. 2013]

Acute- Subacute Onset

Persistent Episodic

Age at onset

Viral 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 appropriate

Paraneoplastic panel (anti-

Hu, anti-Yo, anti-Ri, anti-CMV)

CSF

With vestibular symptoms/signs? (nystagmus, vertigo,

• thers)

Lithium Phenytoin 5-fluorouracil Capecitabine Cytosine arabinoside Metronidazole Amiodarone Hg-Pb-Mn Toluene-benzene derivatives Alcohol-malnutrition

CEREBELLAR

Look for oculomotor abnormalities

Cognitive changes – nystagmus/abducens palsy/papilloedema Cognitive/speech changes – tremor – myoclonus – seizures – sleep probl - psychosis

Episodic ataxias (aut dom)

Attacks precipitated by stress or emotions

EA1 (KCNA1)

Delayed rectifier potassium channel, Kv1.1

Onset: late childhood to adolescence Attacks: secs-mins Interictal myokimia or neuromyotonia with stiffness and weakness during attacks 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, ± headache Interictal 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 Vertebrobasilar insufficiency Syphilis Drugs/Toxins Sensory polyneuropathies

Associated with proprioceptive sensory loss  de-afferentation ataxia

CDDP, cisplatin, carboplatin,

• xaliplatin

Doxorubicin Bortezomib Suramin sodium Thallium Penicillin 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

Rapid progression

Sporadic Inherited

Age at onset

SREAT Paraneoplastic CJD GSS (PRNP gene: P102L most

frequently)

MRI

Thyroid antibodies CSF/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]

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]

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
• ther 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

LEARNING OBJECTIVE 3

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.org National 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?
• Medical conditions: iron deficiency ( Ferrous sulfate + vit.C), end-stage

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

• besity, COPD, DM, IBS
• Neurological diseases: small fibre neuropathies, PD
• Drugs: DR blockers, NSRIs, AEDs (e.g. zonisamide)
• Pregnancy
• 2. Is RLS sufficiently severe to warrant specific treatment?
• Strong evidence (AAN Level A) pramipexole [0.125, 0.25-0.5mg],

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

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

carboxymaltase* [500mg given twice 5 days apart]

• Weak evidence L-dopa*

How do we approach this patient with RLS? Key questions

• 3. Should we target sleep disruption?
• PLMS [PLMI index on PSG] causing frequent awakenings: ropinirole,

pramipexole, rotigotine, pregabalin

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

ropinirole, gabapentin enacarbil, pregabalin

• Subjective sleep measures: gabapentin enacarbil, ropinirole,

pregabalin>pramipexole, rotigotine, L-dopa

• 4. Risk of augmentation?
• Pregabalin / Gabapentin enacarbil
• Pramipexole / Ropinirole / Rotigotine
• L-dopa

How do we approach this patient with RLS? Key questions

• Is the patient not responding to treatments mentioned so far?
• 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?
• Pneumatic compression (inflatable garments and electrical pneumatic pump)

before usual symptom onset likely effective

• NIBS near-infrared stimulation and rTMS (SMA,M1) possibly effective
• tDCS probably ineffective
• Vibrating pads possibly ineffective
• 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]