Canadian Society of Internal Medicine Annual Meeting 2018 Banff, AB W14. Movement Disorders for the Internist Dr. Davide Martino, PhD MD Movement Disorders Program, DCNS, University of Calgary 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 other sources of information or your medical judgment. Conflict Disclosures “I have no conflicts to declare” 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. 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 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] Age at onset With vestibular Viral infections: VZV (children)- symptoms/signs? EBV (adults) (nystagmus, vertigo, MS others) Persistent Cognitive/speech changes – tremor – Look for oculomotor myoclonus – seizures – SREAT sleep probl - psychosis Lithium abnormalities Phenytoin Acute- Paraneoplastic 5-fluorouracil Cognitive changes – nystagmus/abducens Wernicke Capecitabine CEREBELLAR Subacute palsy/papilloedema Cytosine arabinoside Onset Stroke Metronidazole Drugs/Toxins Amiodarone Drug history (CT)/MRI Hg-Pb-Mn Thyroid antibodies Toluene-benzene derivatives (anti-TPO + anti-Tg) Genetic episodic ataxias Alcohol-malnutrition Episodic If appropriate MS Paraneoplastic panel (anti- Stroke Hu, anti-Yo, anti-Ri, anti-CMV) CSF Episodic ataxias (aut dom) Attacks precipitated by stress or emotions EA1 (KCNA1) EA2 (CACNA1A) Delayed rectifier P/Q-type calcium channel alpha 1A subunit potassium channel, Kv1.1 Onset: late childhood Onset: infancy to early adulthood to adolescence Attacks: secs-mins Attacks: hours to days, with vertigo, nausea, ± headache Interictal myokimia or Interictal downbeat nystagmus, ataxia and neuromyotonia with rarely dystonia stiffness and weakness during Responds to acetazolamide or 4- attacks aminopyridine Responds to Allelic to SCA6, IGE, FHM type 1, congenital ataxia and acetazolamide hemiplegic migraine with cerebral edema Cognitive – depression - neuropathy – spastic Subacute Associated with para/tetraparesis combined Vitamin deficiency (B12, E, degeneration proprioceptive sensory folic acid) loss de-afferentation Neurosarcoidosis ataxia Vertebrobasilar insufficiency Acute- CDDP, cisplatin, Persistent Syphilis carboplatin, Subacute oxaliplatin Onset Doxorubicin Drugs/Toxins Bortezomib Sensory • Drug history Suramin sodium polyneuropathies • Vitamin B12 (MMA-Hcy) Thallium and E Penicillin • MRI spine • CXR/CT chest + serum markers of sarcoidosis (SAA, sIL-2R, ACE, KL-6) • Syphilis serology • NCS/CSF, anti-GQ1b Age at onset Cognitive/speech changes – tremor – myoclonus – seizures – SREAT sleep probl - psychosis Sporadic Paraneoplastic MRI Rapid Thyroid progression antibodies CSF/EEG Cognitive – psychosis and agitation - CJD depression Inherited GSS (PRNP gene: P102L most frequently) 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 [Bae et al. J Mov Disord 2014] 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 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 [Bae et al. J Mov Disord 2014] 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 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 LEARNING OBJECTIVE 3 MANAGE RESTLESS LEGS SYNDROME AND KNOW WHICH MEDICATIONS SHOULD NOT BE USED [from sleepdisorders.sleepfoundation.org CASE #1 National Sleep Foundation] 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 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* How do we approach this patient with RLS? 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 How