MOVEMENT DISORDERS

Dr. Rashad Abdul ghani Assistant Professor of Neurology

Exrapyramidal system
This system includes The nonpyramidal motor areas in cerebral cortex

Basal ganglia

and their descending tracts

The basal ganglia (BG) are a group of nuclei situated in the deep part of the cerebrum and upper part of the brain stem These nuclei are

Functions
Premotor and somatosensory areas control the axial and proximal limb muscles and produce subconscious associated automatic movements The basal ganglia control the muscle tone and are essential for performance of fine voluntary movements

Basal ganglia circuit

inhibit
stimulate

Hyperkinetic disorder Hypokinetic disorder

Pathophysiology of basal ganglia disorders can be classified into : Hyperkinetic disorder

Chorea
Firing of VIN

Tremor

Hemiballismus

Hypokinetic disorder

Dystonia is associated with putamenal lesion

Akinesia

Parkinsonism

Rigidity

Movement disorders
A movement disorder impairs the regulation of voluntary motor activity without directly affecting strength, sensation or cerebellar function." Movement disorders typically result from diseases of the basal ganglia and can be classified into Akinetic rigid syndromes (Hypokinesia) Parkinson disease and other parkinsonism (Akinesia / bradykinesia and rigidity). Hyperkinesias (Hyperkinesia) (tremor, chorea, athetosis, ballism, tics, dystonia and myoclonus).

General concepts
Movement Disorder -Term for a physical sign - Term to describe a specific syndrome/condition Either excess of movement or paucity of voluntary and automatic movements, unrelated to weakness or spasticity Diagnosis of movement disorders requires: - Identify the type and pattern of movement - Isolated or accompanied with other neuro signs - Determine probable etiology

A systematic approach to diagnosis in patients presenting with movement disorders

Abdo, W. F. et al. (2010) The clinical approach to movement disorders Nat. Rev. Neurol. doi:10.1038/nrneurol.2009.196

Characteristics to classify movements

Distribution Velocity Amplitude Stereotypy Rythmicity Suppressibility Relationship to position, sleep, activity

Parkinsonism - Akinesia / Bradykinesia

Impaired initiation of movement (Akinesia) Slowness of movement (Bradykinesia) Reduced amplitude of voluntary movement Slow initiating movement on command Loss automatic movements Short shuffling steps Loss spontaneous movement (gestures) Hypomimina (decreased blink) Hypophonia Aprosody Drool (decreased spontaneous swallow)

Rigidity
Increased muscle tone to passive motion Present equally in all direction of the passive movement throughout the range of motion Distinguish from spasticity (velocity dependent) Distinguish from paratonia (inability to relax)

Freezing
Motor act halted transiently (several seconds) Agonists and antagonist muscles are simultaneously and isometrically contracting Start hesitation, turning hesitation, destination hesitation, freeze with obstacle

Parkinson Disease (paralysis agitans)

Parkinson disease (PD) is a progressive neurodegenerative disorder associated with a loss of dopaminergic nigrostriatal neurons. PD is recognized as one of the most common neurological disorders, affecting approximately 1% of individuals older than 60 years. Cardinal features include aymmetrical sresting tremor, rigidity, bradykinesia, and postural instability.

Pathophysiology

normal

Park dis

Epidemiology
The incidence has been estimated to be 4.5-21 cases per 100,000. Prevalence range from 18-328 per 100,000 population . Most studies yielding a prevalence of approximately 120 per 100,000. Male:female ratio 1.5: 1 Age: The incidence and prevalence of PD increase with age. The average age of onset is approximately 60 years

Clinical features:
Onset of PD is typically asymmetric, with the most common initial finding being an asymmetric resting tremor in an upper extremity.

Over time, patients notice symptoms related to progressive bradykinesia, rigidity, and gait difficulty. Symptoms of autonomic dysfunction are common.

Postural instability refers to imbalance and loss of righting reflexes. Its emergence is an important milestone, because it is poorly amenable to treatment and a common source of disability in late disease. Patients may experience freezing when starting to walk (start-hesitation). Dementia generally occurs late in PD and affects 15-30% of patients. Shortterm memory and visuospatial function may be impaired

Parkinson disease

Causes and classification of parkinsonian syndromes: Primary parkinsonism: (77.7%) Parkinson disease: Sporadic and familial. Secondary parkinsonism: (8.2%) Drug-induced: dopamine antagonists and depletors Toxins: Mn, CO, MPTP, cyanide Trauma, Tumour, Vascular: multiinfarct state. Infectious; postencephalitis Metabolic; parathyroid dysfunction, hypoxia Hydrocephalus; normal pressure hydrocephalus

Parkinson plus syndrome: (8.2%) Cortical basal ganglionic degeneration

myoclonus)

(parkinsonism, apraxia,

Dementia syndromes:
Frontotemporal dementia

Alzeheimer disease, Diffuse lewy body disease ,

Multiple system atrophy syndromes: Striatonigral degeneration (pure parkinsonism) Shy-Drager syndrome (parkinsonism, dysautonomia) Sporadic olivopontocerebellar degeneration
(atypical tremor, ataxia, pseudobulbar palsy)

Amyotrophy-parkinsonism Progressive supranuclear palsy

palsy, pseudobulbar palsy, dementia)

(parkinsonism, supranuclear

Heredodegenerative diseases:(0.6%) Willson disease Huntington disease Neuroacanthocytosis Hallervorden-spatz disease

Lab Studies:
No laboratory biomarkers exist for PD. Serum ceruloplasmin concentration is obtained as a screening test for Wilson diseasein in young patients who present with parkinsonian (MRI) and (CT) scan are unremarkable in PD. MRI is useful to exclude multi-infarct state, hydrocephalus, and the lesions of Wilson disease. PET) and (SPECT) may differentiate parkinsons disease from other parkinsonism.

Treatment:
The goal of medical management of PD is to provide control of signs and symptoms for as long as possible while minimizing adverse effects. Medications usually provide good symptomatic control for 4-6 years. After this, many patients develop long-term motor complications including fluctuations and dyskinesia.

Neuroprotective therapy:
To date, no drug has been shown to influence the progression of the disease. A clinical study demonstrated that selegiline delays the need for levodopa therapy in early PD by about 9 months

Symptomatic therapy:
When should symptomatic treatment be started in the treatment of PD? A rational strategy is to start treatment when the symptoms begin to impair activities of daily living or to interfere with social and occupational functioning.

Levodopa, coupled with a peripheral decarboxylase inhibitor (PDI), provides the greatest antiparkinsonian. Dopamine agonists provide symptomatic benefit but lack sufficient efficacy to control signs and symptoms by themselves in later disease.

Early disease treatment strategies Young patients have a longer life expectancy and are more likely to develop motor fluctuations and dyskinesia, so other antiparkinsonian drugs should be used first to delay the introduction of levodopa. This approach is known as dopa sparing strategy.

Medication
Dopamine agonists

PDI

L-dopa

COMT inhibitors

Anticholinergic

MAO-B inhibitors

Amantadine
DA releaser

Surgery
Stereotactic surgery has made a resurgence in the treatment of PD. This is mainly because many patients with advanced PD experience significant disability or adverse effects despite optimal medical management.

Thalamotomy and chronic thalamic stimulation are effective in reducing medically refractory tremor. Pallidotomy: This procedure is effective in reducing contralateral dyskinesia.

Thalamic deep brain stimulation (DBS) had demonstrated benefit for contralateral bradykinesia and dyskinesia.

Transplantation
Neural transplantation is a potential treatment for PD. Multiple sources of dopamine-producing cells, including fetal nigral cells, sympathetic ganglia, carotid body glomus cells have been studied. In animal PD models, fetal nigral dopaminergic cells have been shown to form synaptic connections that exhibit relatively normal electrical firing patterns, and improve motor function.

Tremor
Non-purposeful, rhythmic, patterned to and fro oscillation produced by regular and sequential contraction of agonistic and antagonistic muscles.
Clinical classification: Physiologic tremor Rest tremor Action tremor during voluntary contraction muscles a-Postural tremor voluntarily maintained against gravity b-Kinetic tremor during any voluntary movement -Simple kinetic tremor during non target directed voluntary movement -Intention tremor with increasing amplitude at end of movement c- Taskspecific tremor during specific activity

Eatiological classification of tremor

Enhanced physiologic tremor, such as medications, substances such as caffeine, fever, and anxiety. Essential tremor Parkinsonian tremor Dystonic tremors Cerebellar tremor Drug-induced tremors (antidepressants, especially tricyclics, beta-agonists, dopamine, lithium, metoclopramide, Na valproate, neuroleptics, thyroid hormones). Metabolic: (B-12 deficiency, Hyperthyroidism, Hyperparathyroidism Hypocalcemia, Hyponatremia, Kidney disease, Liver disease). Toxic: Alcohol, Arsenic, Caffeine, Lead, Nicotine, Withdrawal of alcohol , cocaine.

Psychogenic tremor

Essential tremor Essential tremor (ET) is the most common movement disorder. It is a syndrome characterized by a slowly progressive postural and/or kinetic tremor, usually affecting both upper extremities. The pathophysiology of ET is not known.

Epidemiology: The prevalence: 0.3-5.6% of the general population. The prevalence of ET increases with age. Age at onset has bimodal peaks- one in late adolescence to early adulthood and a second in older adulthood.

Clinical features:
Tremor usually begins in one upper extremity and soon affects the other. In about 30% of cases, tremor involves the cranial musculature. The tremor is characteristically postural and kinetic. Fifty to sixty percent have a family history of ET.

Treatment: Primidone and propranolol are the cornerstones of maintenance medical therapy for ET.

Chorea, Athetosis, Ballism

Chorea: rapid, jerky, non-rhythmic, non-patterned aimless proximal and distal involuntary movements (dancing-like). Flow from one part body to another Unpredictable in timing, direction, distribution (random) Athetosis: mixture of slow, twisting and writhing involuntary movements (snake-like)which mainly distal. Often blends with chorea (choreoathetosis) Ballism: Violent, flinging limb movements, which are mainly proximal.

Choreiform and ballistic movement disorders Causes and classification of chorea

Idiopathic Hereditary - Huntington disease, neuroacanthocytosis, Dentatorubropallidoluysian atrophy (DRPLA), ataxia-telangiectasia, familial calcification of basal ganglia, Hallevorden-Spatz disease, Mitochondrial cytopathies. Hereditary (metabolic) - Wilson disease, Lesch-Nyhan disease, phenylketonuria, acute intermittent porphyria

Other metabolic and endocrine disorders - Kernicterus, hyperthyroidism hypoparathyroidism, hypoglycemia, nonketotic hyperglycemia, chorea gravidarum, hypomagnesemia, chronic nonfamilial hepatic encephalopathy, anoxic encephalopathy.

Infectious - Sydenham chorea, encephalitides, subacute sclerosing panencephalitis, syphilis, HIV infection, cerebral toxoplasmosis, Creutzfeldt-Jakob disease, subacute bacterial endocarditis.
Drug induced - Neuroleptics, levodopa, anticholinergics, oral contraceptives, antihistamines, amphetamines, cocaine, phenytoin, tricyclics. Toxins - Alcohol intoxication and withdrawal, carbon monoxide, manganese, mercury.

Vascular Cerebrovascular disease (ischemic or hemorrhagic), vasculitidis. Immunologic - Systemic lupus erythematosus, primary antiphospholipid antibody syndrome, multiple sclerosis, postcardiac transplantation, postvaccination
Tumors - Primary, metastaticc

Sydenhams (rheumatic) chorea:

Sydenham chorea is a major manifestation of acute rheumatic fever, seen in up to 10 per cent of patients after streptococcal infection in endemic areas. It arises some months after the acute illness and is largely confined to children 5-15 years of age. The condition is considered to be the result of auto-antibodies reacting with the caudate nucleus.

Clinical features
Rheumatic chorea is characterized by muscle weakness and the presence of chorea. The patients have the milkman grip sign, clumsy gait, and dysarthric speech. Psychological symptoms are equally prominent and typically precede the appearance of even the most subtle choreiform movements.

Lab studies: Antistreptococcal antibody titers may no longer be elevated at presentation. Neuroimaging: Most cases of Sydenham chorea show no abnormalities.

Treatment: The most widely used agents in treatment of chorea are the neuroleptics. GABAergic drugs, such as clonazepam and gabapentin, can be used as adjunctive therapy. Intravenous immunoglobulin and plasmapheresis may shorten the course of the illness

Huntingtons disease Huntingtons disease is inherited as an autosomal dominant. The relevant gene has been mapped to the short arm of chromosome 4.

Neuropathology The most striking neuropathology in HD occurs within the neostriatum (medium spiny neurones), in which gross atrophy of the caudate nucleus and putamen is accompanied by astrogliosis.

The genetic basis of HD is the expansion of a cysteine-adenosine-guanine (CAG) repeat encoding a polyglutamine. The increase in polyglutamine seems to prevent the normal turnover of the protein, resulting in aggregation of the protein with accumulation in the cytoplasm and nucleus. The prevalence of HD: 4.1-8.4 per 100,000 people.

Clinical features: In most, onset is in the third or fourth decade but about 10 per cent of cases present before the age of 20 years. Juvenile onset cases are more likely to show paternal transmission, a fulminant course, and a predominantly rigid picture compared to late-onset cases.

The clinical features of HD include a movement disorder, a cognitive disorder, and a behavioral disorder. Patients may present with one or all disorders in varying degrees. Chorea is the most common movement disorder seen in HD. As the disease progresses, chorea coexists with and gradually is replaced by dystonia and parkinsonian features, such as bradykinesia, rigidity, and postural instability. Other late features are spasticity, clonus, and extensor plantar responses.

Cognitive decline is characteristic of HD.TThe dementia syndrome associated with HD includes early onset behavioral changes. Slowing of cognition, impairment of intellectual function, and memory disturbances are seen later. Other features include ataxia, a general motor clumsiness, an inability to sustain muscle contraction and personality change. Saccadic eye movements are slowed. .

Juvenile HD (Westphal variant), defined as having an age of onset of younger than 20 years, is characterized by parkinsonian features, dystonia, long-tract signs, dementia, epilepsy, and mild or even absent chorea.

Investigations Investigative findings, while often suggestive, do not provide specific confirmation of the diagnosis.
MRI
CT SCAN

Genetic testing

SPECT

Treatment
No specific treatment. Symptomatic treatment may improve the quality of life and prevent complications. The choreic movements can be controlled by the use of neuroleptic agents.

Tics
Tics: rapid lightening-like brief semi-purposeful, repetitive and stereotyped movements. Abnormal movement (motor tics) or abnormal sounds (phonic tics) or both (tourette syndrome) Precede by urge , can be suppressed for various periods of time, inner tension, relieved by increased burst of tics

Primary tic disorder Transient Motor or vocal

15% children (male>female) Mild usually single movement

Secondary tic disorders Drugs

- CNS stimulants: amphetamines,
methylphenidate, pemoline, cocaine -Neuroleptics: tardive tics Levodopa Anticonvulsants: carbamazepine, lamotrigine, phenytoin, phenobarbital

Chronic single tic disorder

Motor or vocal > 1 year

Hereditary: HD, Wilsons, others Adult onset (recurrent) tic Neurodevelopmental disorders Tourette syndrome Perinatal injury, chromosomal Disorders Motor and vocal > 1 year Brain injury
Onset < 21 year old
Stroke, encephalitis, trauma, CO poison

Infections
Sydenhams chorea, PANDAS Postviral encephalitis, lyme, HIV

Gilles de la Tourettes syndrome

Isolated tics are quite common in childhood, usually remitting within a year or so of onset. Multiple tics are classified as motor and vocal tics. Where they are accompanied by vocalization, the diagnosis of Gilles de la Tourettes syndrome is made .

Clinical features This condition usually begins in the first decade of life, and is more common in girls. Associated problems include echolalia, echopraxia and various behavioural disturbances. Haloperidol has proved the most effective drug for the treatment of this condition.

Dystonia
Dystonia: involuntary, sustained muscle contractions, causing twisting and repetitive movements and abnormal postures. Progress to prolonged abnormal postures Repeatedly involve the same group of muscles (unlike chorea) Relatively long duration (compared to myoclonus and chorea) Agonists and antagonists contract simultaneously

Dystonia
Eatiological classification Idiopathic or primary (Familial or sporadic) Dystonis plus syndrome Secondary as a consequence of focal brain damage Neurodegenerative dystonia

Anatomic Distribution of Primary Torsion Dystonia

Focal Single Body Site

Segmental
Multifocal Generalized Hemidystonia

Contiguous body regions

Multiple, noncontiguous body sites Leg involvement with other body sites Unilateral

Causes of dystonias:
Idiopathic or primary torsion dystonia Secondary etiologies of dystonia
Vascular Cerebrovascular, AVM Perinatal cerebral injury Infectious Viral encephalitis SSPE AIDS Creutzfeldt-Jakob disease Trauma Head trauma Peripheral trauma Tumor Brain tumor Toxins Manganese, carbon monoxide, carbon disulfide, methanol

Metabolic Drugs Kernicterus Levodopa, dopamine agonists, Wilson disease antipsychotics, metoclopramide, Homocystinuria fenfluramine, flecainide, ergot Metachromatic leukodystrophy agents, anticonvulsant agents, Neuronal ceroid lipofuscinosis certain calcium channel blockers Niemann-Pick disease, type C Primary antiphospholipid antibody syndrome Mitochondrial encephalopathies Lesch-Nyhan syndrome Structural Atlanto-axial subluxation Syringomyelia Arnold-Chiari malformation Congenital Klippel-Feil syndrome

Dystonia plus syndromes

Myoclonus dystonia Rapid-onset dystonia parkinsonism Xlinked dystonia parkinsonism (Lubag)

Neurodegenerative
Progressive supranuclear palsy Multiple systems atrophy Corticobasal-ganglionic degeneration Hallervorden-Spatz disease Neuroacanthocytosis Spinocerebellar ataxia (SCA), types 1, 2, 3 Ataxia telangiectasia Huntington disease Dentatorubropalidoluysian atrophy

Wilson disease
Wilson disease, or hepatolenticular degeneration, is a neurodegenerative disease of copper metabolism. Wilson disease is an autosomal recessive inherited condition caused by mutations of a gene being located on the long arm of chromosome 13.

Pathophysiology: Wilson disease involves loss of ability to export copper from the liver into bile and to incorporate copper into hepatic ceruloplasmin. Consequently, copper accumulates in the liver, brain, kidney, and cornea. Pathological changes include cirrhosis of the liver and atrophy of the putamen where cavitation may appear.

Microscopically there is neuronal cell loss together with astrocytic proliferation.

Epidemiology Incidence is 1 in 35,000-100,000 live births. Age: The onset of liver disease is usually at age 816 years. Neurological symptoms are rare before age 12 years.

Clinical features About 40-50% of patients present with liver disease and 35-50% with neurological or psychiatric symptoms. Kayser-Fleischer rings are almost always present when the patient has neurological symptoms.

Neurological Wilson disease may develop very gradually, sometimes with acute deterioration. There are three main types: Dystonic type Akinetic-rigid form Cerebellar pseudosclerotic type

A dystonic type presents with dysarthria, dysphagia and drooling of saliva due to dystonia of the face and bulbar musculature. Dystonia of the limbs lead to rigidity, abnormal posture and a dystonic gait.

An akinetic-rigid form presents with prominent resting or postural tremor and variable bradykinesia and rigidity. The tremor of the arms may be very severe (wing beating tremor). A cerebellar pseudosclerotic type presents with gait ataxia, dysarthria, limb ataxia and titubation of head.

Psychiatric manifestation include hyperkinetic behavior, irritability or emotional lability, psychosis, abnormal behavior, personality changes and depression.

Lab Studies: No one test is completely reliable; diagnosis depends upon a high index of suspicion and supporting laboratory abnormalities. Low serum copper level. Low serum ceruloplasmin level. Increased urinary copper level. Liver biopsy Reveals evidence of liver cirrosis with increased hepatic copper.

Treatment Treatment is based on the use of D-penicillamine, trientine or zinc. The former two are chelating agents; zinc acts by blocking uptake of copper from the intestine.

Myoclonus
Myoclonus: Sudden brief shock like involuntary purposeless movement from muscle contraction (positive myoclonus) or inhibition (negative myoclonus)
Rhythmic or arrhythmic Generalized, focal or multifocal Stimulus sensitive or action sensitive Symmetric or asymmetrical Involuntary movement no preceding urge as seen in Tic. Arise from any point in neuroaxis Cortex can be associated with seizures Subcortical Brainstem Spinal cord Peripheral nerve

 Physiologic hypnic jerk, hiccup, benign infantile myoclonus Epileptic epilepsia partialis continua, infantile spasms, juvenile myoclonic epilepsy Progressive myoclonic epilepsy inborn errors metabolism, lysosomal storage diseases, mitochondrial disorders, etc.
Heterogeneous group of disorders characterized by epilepsy, myoclonus, progressive neurological deterioration

Differential diagnosis of Myoclonus

Symptomatic Post hypoxic

Post traumatic Myoclonic dementias CJD, AD, LBD Toxic Metabolic Drug induced Post infectious Inflammatory Neurodegenerative basal ganglia disorders (CBGD, PD,