Neuroimmunology + Movement Disorders Flashcards

Question

Characteristics of multisystem atrophy

Answer 1

- Accumulation of alpha synuclein - Triad of autonomic failure, parkinsonism, cerebellar signs - Primary autonomic failure: Postural hypotension, urinary retention, constipation, erectile dysfunction IX: Hot cross bun sign on MRI in pons (atrophy) - cross shaped hyperintensity on T2 weighted axial images of pons TX - Levodopa: often exacerbates orthostatic hypotension - Orthostatic hypotension - non pharm, fludrocortisone, midodrine - Urinary dysfunction: oxybutynin, solifenacin, mirabegron

Answer 2

- Tau - Parkinsonism - rigidity, dystonia - Limb apraxia/ Alien limb phenomenon - Myoclonus - Cortical sensory signs - neglect, dysgraphaesthesia, astereognosis - Cognitive impairment - Speech apraxia or nonfluent aphasia Bilateral atrophy of basal ganglia Tx: - Botulin toxin for dystonia

Answer 3

``` Diagnostic criteria URGE - urge to move legs usually with dysaethesias - rest induced - gets better with activity - evening or night worsening ``` Associations - Poor sleep hygiene - Coffee, stimulants - Iron deficiency - SSRis and dopamine antagonists can worsen RLS tx - L dopamine, dopamine agonists (pramipexole, rotigotine patch), gabapentin/pregablin, iron supplementation Restless legs syndrome (RLS) is a syndrome of spontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population. Males and females are equally affected and a family history may be present Clinical features uncontrollable urge to move legs (akathisia). Symptoms initially occur at night but as condition progresses may occur during the day. Symptoms are worse at rest paraesthesias e.g. 'crawling' or 'throbbing' sensations movements during sleep may be noted by the partner - periodic limb movements of sleeps (PLMS) ``` Causes and associations there is a positive family history in 50% of patients with idiopathic RLS iron deficiency anaemia uraemia diabetes mellitus pregnancy ``` The diagnosis is clinical although bloods such as ferritin to exclude iron deficiency anaemia may be appropriate Management simple measures: walking, stretching, massaging affected limbs treat any iron deficiency dopamine agonists are first-line treatment (e.g. Pramipexole, ropinirole) benzodiazepines gabapentin

Answer 4

- Inherited movement disorder - X linked DOMINANT inheritance - Associated with FMR1 protein deficiency - CGG repeats - Cause intellectual disability, seizures, autism in early childhood Clinical Features - Intention tremor - Ataxia - Parkinsonism - Peripheral neuropathy - Autonomic disturbance - Cognitive impairment - Mood disturbance Pathology: intranuclear neuronal and astrocytic inclusions MRI findings: white matter lesions involving middle cerebellar penduncles

Answer 5

- Autosomal dominant - Increased number of trinucleotide CAG repeats located on chromosome 4 (huntingtin gene) leads to degeneration in striatal neurons >37 repeats: symptomatic - Anticipation: greater number of repeats, earlier onset - Caudate atrophy - GABAergic neurons Clinical Features - Hyperkinetic movement disorder - Cognitive impairment - Depression - Psychosis - Oculomotor dysfunction Motor: - Dystonia (can be first sign) - Chorea, face and axial - Bradykinesia and rigidity (late stage or westphal variant) Cognitive - Can predate motor, can vary in severity - Executive function Most common cause of death is pneumonia and then suicide. TREATMENT - Chorea: tetrabenazine, AP (risperidone, olanzapine) - Parkinsonian feature: Levodopa - Antidepressants - Antipsychotics, mood stabilisers

Answer 6

Overuse of serotonin drugs - SSRI: fluoxetine, citalopram, sertraline - SNRI: duloxetine, venlafaxine - Monoamine oxidase inhibitors: Phenelzine, Selegiline - Tricyclic antidepressants amitryptilline - Opioids: methadone, tramadol, oxycodone - Antiemetics: ondansetron, maxalon - MDMA, cocaine - St johns warts ``` HARM - Hypertherma- Autonomic instability - Rise in blood pressure - Myoclonus ``` Clinical Features Triad of mental status changes, neuromuscular hyperactivity, autonomic hyperactivity - Mental changes: agitation, hypervigilance, pressure speech delirium - Neuromuscular Hyperactivity: myoclonus, tremor, hyperreflexia, rigidity and clonus prominently in LL - Autonomic Hyperactivity: hypertension, tachycardia, diaphoresis, shivering, temperature > 40 ``` Tx Discontinuation of serotonergic drugs Supportive Care: Cooling measures: ice packs, cold compress Antihypertensives, fluid replacement Benzodiazepines for sedation Cyprohepatidine Serotonin antagonist Used for serotonin syndrome that do not respond to supportive care ```

Answer 7

- Neuroleptic malignant syndrome (NMS) is a severe disorder caused by an adverse reaction to medications with dopamine receptor-antagonist properties or the rapid withdrawal of dopaminergic medications. - More common in 1st generation antipsychotics - Rapid escalation, multiple drugs, long acting forms Medications: - Typical antipsychotics: haloperidol, droperidol - Atypical: clozapine, olanzapine, risperidone, aripirazole, quetiapine - Other dopamine antagonist: metoclopramide, prochlorperazine, promethazine Clinical Features - Muscle rigidity (lead pipe rigidity, tremor - Autonomic dysfunction: hyperthermia, tachycardia - Altered conscious state Elevated CK (rhabdo) Leukocytosis Elevated transaminases FALTER: fever, autonomic instability, leukocytosis, tremor, elevated enymes (CK, transaminases), rigor Treatment: - Discontinouation of drug - Supportive - Dantrolene: muscle relaxant - Alternative: bromocriptine, benzos

Answer 8

Wernicke and Korsakoff syndrome: medial thalamus and mammillary bodies of the hypothalamus Hemiballismus - Unilateral violent flinging movements of limbs - Lesions of the contralateral SUBTHALAMIC NUCLEUS of the basal ganglia The ballisic movements primarily affect the proximal limb musculature whilst the distal muscles may display more choreiform-like movements Symptoms may decrease whilst the patient is asleep. Antidopaminergic agents (e.g. Haloperidol) are the mainstay of treatment - Huntington chorea: stratium (caudate nucleus) of the basal ganglia Chorea is caused by damage to the basal ganglia, in particular the Caudate nucleus - Parkinsons disease: substantia nigra (pars compacta) of the basal ganglia - Kluver bucy syndrome - hypersexuality, hyperorality, hyperphagia, visual agnosia: amygdala Hemiballismus – sudden flailing movements of contralateral limbs – lesion STN Chorea – dancelike – jerky, purposeless movements of limbs, face & tongue, eg. Huntington’s chorea (genetic – autosomal dominant) - results from degeneration of D2 GABA cells in striatum (which are part of the indirect pathway). Athetosis – slow writhing movements trunk and proximal limbs with varying degrees of spasticity, eg. cerebral palsy. Commonly combined with chorea – known as choreoathetosis.

Answer 9

Dopamine antagonist Typical Ap: haloperidol, chlorpromazine Atypical: risperidone, olanzapine, aripiprazoel Antiemetics: metoclopramide Drug-induced parkinsonism may be distinguished from idiopathic Parkinson disease on the basis of the symmetry of symptoms and the absence of typical nonmotor features.

Answer 10

Essential Tremor - Bilateral, largely symmetrical postural and kinetic tremor involving hands and forearms - Slow progression - Begins later in life 50-60s - May have concomitant head and jaw tremor (yes tremor) - Improves with alcohol - Familial in 50%, autosomal dominant - Involves cerebellar-thalamic circuit and dentate nucleus-red nucleus-inferior oliv circuit Tx: - propranolol and primidone - Topiramide - Clonazepam - DBS: ventral intermediate nucleus of the thalamus - Ultrasound thalamotomy

Answer 11

Wilson disease

Answer 12

Dystonia involves sustained stereotyped and directional twisting and posturing movements of various body parts. Medications include anticholinergics, benzodiazepines, baclofen - Botox injection - Trihexyphenidyl (Artane) - tremor dystonia

Answer 13

Chorea consists of random, nonrepetitive, flowing dance like movements. Can be caused by antipsychotics, estrogen containing drugs, endocrine derangement (thyrotoxicosis, acute hyperglyacemia, pregnancy, streptococcal infection, autoimmune (sle, aps) Chorea describes involuntary, rapid, jerky movements which often move from one part of the body to another. Slower, sinuous movement of the limbs is termed athetosis. Chorea is caused by damage to the basal ganglia, especially the caudate nucleus. Causes of chorea - Huntington's disease, Wilson's disease, ataxic telangiectasia - SLE, anti-phospholipid syndrome - rheumatic fever: Sydenham's chorea - drugs: oral contraceptive pill, L-dopa, antipsychotics - neuroacanthocytosis - pregnancy: chorea gravidarum - thyrotoxicosis - polycythaemia rubra vera - carbon monoxide poisoning - cerebrovascular disease

Answer 14

- Unilateral, rest, postural, movement and worse on intention - Lesion in the midbrain tegmentum outside the red nucleus especially in the superior cerebellar peduncle or posterior part of thalamus, interrupting cerebellar outflow pathways - Horrendous tremor, super severe cerebellar tremor - Wilsons disease, stroke, MS

Answer 15

- Sustained or intermittent muscle contractions causing abnormal movements, often repetitive, patterned, twisting or tremulous - Lead to no-no tremor - Can worsen when you do an action that is opposite the dystonia - Can have task dependent dystonia Cervical dystonia Doapminergic + cholinergic involement TX - Levodopa trial - dopa responsive dystonia - Clonazepam, trihexyphenidyl (generalised) - Botulinum toxin (isolated) - DBS

Answer 16

• Leber: mitochondrial condition leading to optic neuropathy ○ Inherited from maternal line ○ Occurs in high oxygen dependent areas - optic, ear, liver, small fibre neuropathy ○ PAINLESS progressive bilateral sequential vision loss, bilateral optic disc swelling ○ Can be very acute Primarily affects men

Answer 17

Friedreich's ataxia is the most common of the early-onset hereditary ataxias. It is an autosomal recessive, trinucleotide repeat disorder characterised by a GAA repeat in the X25 gene on chromosome 9 (frataxin). Friedreich's ataxia is unusual amongst trinucleotide repeat disorders in not demonstrating the phenomenon of anticipation. The typical age of onset is 10-15 years old. Gait ataxia and kyphoscoliosis are the most common presenting features. ``` Neurological features absent ankle jerks/extensor plantars cerebellar ataxia optic atrophy spinocerebellar tract degeneration ``` Other features hypertrophic obstructive cardiomyopathy (90%, most common cause of death) diabetes mellitus (10-20%) high-arched palate Friedreich's ataxia is a genetic progressive neurodegenerative disorder. It causes degeneration of the corticospinal tracts, dorsal columns and spinocerebellar tracts, as well as hypertrophic cardiomyopathy and diabetes. Symptoms include ataxia, slurred speech, spasticity, dysphagia, limb sensory loss and vision and hearing loss. Symptoms are usually apparent by adolescence.

Answer 18

For first-line treatment: - if the motor symptoms are affecting the patient's quality of life: levodopa - if the motor symptoms are not affecting the patient's quality of life: dopamine agonist (non-ergot derived - pramipexole, ropinirole, rotigotine), levodopa or monoamine oxidase B (MAO‑B) inhibitor Monoamine oxidase B inhibitos EG:: Rasagiline, Selegiline New Medication: - Safinamide - MAO B inhibitor + glutamate release inhibitor - leads to increased ON time without troublesome dyskinesias

Answer 19

Dystonia - fixated position Athetosis - Snake-like writhing (slow) Choreiform - Like a dance choreographer Ballistic/Ballismus/Hemiballismus - Fast flinging movements, can injure themselves or others 'like a ballistic missile' (memorisation method)

Answer 20

Causes of Parkinsonism • Parkinson's disease • drug-induced e.g. antipsychotics, metoclopramide* • progressive supranuclear palsy • multiple system atrophy • Wilson's disease • post-encephalitis • dementia pugilistica (secondary to chronic head trauma e.g. boxing) • toxins: carbon monoxide, MPTP *Domperidone does not cross the blood-brain barrier and therefore does not cause extra-pyramidal side-effects

Answer 21

Intention tremor is the result of dysfunction of the CEREBELLUM, particularly on the same side as the tremor in the lateral zone, which controls visually guided movements. Depending on the location of cerebellar damage, these tremors can be either unilateral or bilateral.

Answer 22

In essential tremor, an area of the brain called the thalamus sends faulty electrical signals causing the hands, arms, head or voice to shake uncontrollably. While both intention and essential tremor are characterized by muscle oscillations, intention tremors are slower, zigzag-like movements which are evident when intentionally moving towards a target, whereas an essential tremor is a neurological disorder that can lead to tremors without accompanying intentional movements.

Answer 23

- Intention tremors are a type of kinetic tremor, which become apparent during voluntary and intentional movement. - They typically affect the upper limbs, but can also involve other body parts. Causes: - MS (most common) - Cerebellar lesion - Hereditary disorders, metabolic conditions, psychological conditions, or exposure to toxic substances.

Answer 24

Safinamide - MOA B inhibitor + glutamate release inhibitor - Increased "on" time without troublesome dyskinesias Potential Neuromodulatory Treatments - Glucagon like peptide 1 receptor agonist: Exenatide - Used in T2DM - Neuroprotective effects in animal models - Improvement in motor symptoms in "off" state Future Treatment - Stem cell therapy Foetal ventral mesencephalon dopamine producing neuroblasts

Answer 25

Characteristic tremor PLUS: - Mild neurological signs, eg: impaired tandem gait, dystonic posturing, cognitive impairment - Action PLUS resting tremor

Answer 26

Motor and Vocal tics - Blinking, grimacing, shrugging, head jerking - Grunting, barking, throat clearing, sniffing - Complex: echo/coprapraxia, echo/copralalia (vulgar writings/involuntary profane drawings) - Abilit to suppress, urge to perform Associated with ADHD, OCD, learning disorder, mood disorder Tx: - Habit reversal training - Tetrabenazine, Risperidone - ADHD - clonidine - OCD -SSRI

Answer 27

Tardive Dyskinesia: delayed onset of orofacial dyskinesia in the context of antipsychotic use Drug induced parkinsonism: symmetrical extrapyramidal signs Tx: - Reduce antipsychotic - Change to atypical antiosychotic - Tetrabenazine, Benztropine

Answer 28

- Dysarthria - Dystonia - Tremor - Rigidity - Chorea - Ataxia - Behaviour, cognitive and mood disturbance - Liver disease Mean Age of Onset - Hepatic: 9-13yo - Neurological 15-21yo - Autosomal RECESSIVE, ATP7B gene - Disorder of copper metabolism Diagnosis - Low serum ceruloplasmin - High urinary copper - Kayser Fleischer Rings - High copper on liver biopsy Treatment - Chelating Agents: penicillamine or trientene + zinc - Levodopa - Antipsychotics + antidepressants - Liver transplant