This document discusses various parkinsonian disorders including Parkinson's disease, atypical parkinsonian disorders (Progressive supranuclear palsy, Multisystem atrophy, Corticobasal degeneration), and other causes of parkinsonism such as medications, cerebrovascular disease, Wilson's disease, and Huntington's disease. It provides details on the clinical features, investigations, pathology, and management of these conditions.

1. NEUROLOGY
Dr. Rami Abo Ali
Neurology
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Dr.
Rami
Abo
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2. THE ATYPICAL PARKINSONIAN
DISORDERS
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3. DIFFERENTIAL DIAGNOSIS OF PARKINSON’S
DISEASE
 Parkinsonism refers to a syndrome where the
clinical features resemble Parkinson’s disease but
have a different pathological basis.
 Hypothyroidism and depression may superficially
mimic Parkinson’s disease but will have no
physical signs of parkinsonism.
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4. CAUSES OF PARKINSONISM INCLUDE :
 Medications : dopamine antagonists (e.g.
phenothiazines, reserpine, haloperidol), lithium
 Trauma : subdural haematomas, repetitive head injury,
e.g. boxing
 Cerebrovascular disease: lacunar infarcts of the basal
ganglia and small vessel disease of the cerebral white
matter
 Hydrocephalus or tumor
 Infections such as encephalitis lethargica "sleepy
sickness" and Japanese B encephalitis
 Atypical parkinsonian disorders: multisystem atrophy,
progressive supranuclear palsy and corticobasal
degeneration
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5. DIFFERENT
 Idiopathic Parkinson’s disease can be
differentiated from other parkinsonian
syndromes by:
 An excellent response to L-dopa
 Asymmetrical onset of the bradykinesia, rigidity
and usually tremor
 Absence of other neurological system
involvement, e.g. pyramidal system.
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6. THE ATYPICAL PARKINSONIAN
DISORDERS
 The atypical or ‘Parkinson’s plus’ syndromes
refers to other forms of parkinsonism that have
clinical features that are not typical of
Parkinsons’s disease.
 These include symmetrical parkinsonism, little or
no tremor and a poor or an absent response to L-
dopa therapy.
 There are also additional neurological symptoms
and signs
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7. THE ATYPICAL PARKINSONIAN
DISORDERS
 Incloudes :
 Progressive supranuclear palsy
 Multisystem atrophy
 Corticobasal degeneration
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8. PROGRESSIVE SUPRANUCLEAR PALSY
 PSP is a rare condition with a mean age of onset of 63
years, and an average survival of 7 years.
 It is characterized by
 Gait problems and falls early on,
 Symmetrical parkinsonism
 A prominence of axial features
 Cognitive decline, dysarthria, dysphagia
 A striking supranuclear gaze palsy that initially affects
vertical gaze, but subsequently may affect all eye
movements.
 The speed and range of voluntary eye movements are
limited and can be overcome with the ‘doll’s head’ or
oculocephalic manoeuvre which demonstrates a full
range of eye movements. 8
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10. PROGRESSIVE SUPRANUCLEAR PALSY
 The pathway from the cranial nerve nuclei
responsible for ocular movements to the extraocular
muscles is intact, and the pathology lies above the
nucleus (i.e. supranuclear).
 There may be an astonished facial expression with
overreaction and increased wrinkling of the frontalis
muscle
 There is usually a history of falls backwards early in
the disease and PSP should be strongly considered in
any patient with parkinsonian signs who suffers
frequent falls within the first few years of onset.
 A pseudobulbar palsy develops insidiously with
dysarthria, dysphagia and prominent emotional
lability.
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11. PROGRESSIVE SUPRANUCLEAR PALSY
 Cognitive decline is common, particularly with
frontal release signs and dysexecutive features.
 Pathological findings include neuronal loss,
gliosis and aggregates of tau protein and
neurofibrillary tangles in the brainstem, basal
ganglia and cerebral cortex.
 The diagnosis is based on the clinical features
and the MRI may identify atrophy of the
midbrain (the ‘hummingbird’ sign) and superior
cerebellar peduncles.
 There is usually little response to treatment with
L-dopa, but amantadine may be useful. 11
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the ‘hummingbird’ sign

14. MULTISYSTEM ATROPHY
 MSA is a neurodegenerative disorder characterized by
parkinsonism and cerebellar signs, or autonomic
failure.
 It is rare, with a mean age of onset of 57 years
 An average survival of 7 years.
 Two forms are recognized;
 MSA-P
 MSA-C.
 MSA-P is associated with:
A. Asymmetrical parkinsonism that is poorly
responsive to L-dopa
B. Autonomic failure.
 includes a postural drop in blood pressure, loss of sweating,
urinary incontinence or retention and early erectile
dysfunction.
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15. MULTISYSTEM ATROPHY
 In MSA-C, a cerebellar ataxia predominates with autonomic
failure
 Other features that occur in MSA and may help to
differentiate it from other parkinsonian conditions include
 Postural instability
 Orofacial dystonia
 Anterocollis
 Myoclonus that manifests as an irregular and jerky tremor
of the upper limbs
 Pyramidal signs (spasticity, weakness, slowing of rapid
alternating movements, hyperreflexia, and a Babinski sign)
 Abnormal respiratory patterns (e.g. stridor, gasps and sleep
apnoea),
 Prominent emotional lability referred to as emotional
incontinence.
 Cognitive decline is not a feature of MSA.
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17. MULTISYSTEM ATROPHY
 The pathological hallmark of the disease is glial
cytoplasmic inclusions that contain alpha-synuclein
in the basal ganglia, cerebellum, pons/medulla and
motor cortex.
 Cell loss and gliosis is also seen in Onuf’s nucleus in
the spinal cord which underlies the intrusive
dysfunction of bladder and bowel.
 The diagnosis is a clinical one which can be supported
by an MRI that may show degeneration of the middle
cerebellar peduncles and pons (‘hot-cross bun’ sign).
 Abnormal autonomic function tests may also aid
diagnosis.
 Treatment is essentially symptomatic, though
amantadine and L-dopa should be trialled 17
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19. CORTICOBASAL DEGENERATION
 CBD is a rare disorder that is characterized by
strikingly unilateral involvement with rigidity and
dystonia in an arm.
 There is no tremor, but other parkinsonian symptoms
and signs are often prominent in addition to cognitive
and visuospatial neglect, limb apraxia (inability to
make purposeful movements) and myoclonus of the
affected arm.
 Dysphasia and dysphagia may also occur.
 Patients also report ‘alien limb’ phenomenon where
the arm appears to have a mind of its own and also
appears alien.
 The arm may eventually become functionally useless.
 Initial symptoms typically begin at the age of 60
years. 19
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21. CORTICOBASAL DEGENERATION
 Eventually, both sides are affected as the disease
progresses.
 Patients usually become bed-bound through
immobility and die within 6–8years.
 Treatment is mainly supportive and L-dopa has
little or no effect.
 Post-mortem examination of the brain
demonstrates tau inclusions.
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23. OTHER PARKINSONIAN SYNDROMES
 Includes :
 Medication-induced parkinsonism
 Cerebrovascular disease
 Wilson’s disease
 Huntington’s disease
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24. MEDICATION-INDUCED PARKINSONISM
 Medications that have dopamine antagonist effects
can cause a parkinsonian syndrome with
bradykinesia and rigidity and tremor.
 The neuroleptics which include the phenothiazines
(e.g. chlorpromazine), butyrophenones (e.g.
haloperidol), thioxanthenes (e.g. flupentixol) and
substituted benzamides (e.g. sulpiride) can commonly
cause parkinsonian, or extrapyramidal side effects.
 These typically resolve after drug withdrawal,
though some of the effects may be irreversible despite
discontinuing the offending drug.
 Other commonly used dopamine receptor blocking
drugs include prochlorperazine, metoclopramide and
flunarizine, which are commonly used to treat vertigo,
nausea and vomiting, and migraine.
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25. CEREBROVASCULAR DISEASE
 The pathological basis of cerebrovascular disease causing
parkinsonism is usually multifocal small vessel disease,
particularly subcortical ischaemia and lacunar infarcts.
 Patients often have a degree of cognitive impairment and
pyramidal signs in the limbs with symmetrical
bradykinesia and rigidity and little resting tremor.
 It typically affects the lower limbs and is sometimes called
‘lower limb parkinsonism’.
 Patients typically have a small-stepped gait called ‘marche
a petit pas’ with an upright stance with normal arm swing
(as compared with the stooped posture of Parkinson’s
disease) and an unsteady wide-based gait.
 Treatment is aimed at secondary prevention by treating
underlying cardiovascular risk factors, especially
hypertension 25
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26. WILSON’S DISEASE
 Wilson’s disease is an inherited autosomal recessive
disorder of copper metabolism, resulting in low levels
of the copper-binding protein ceruloplasmin.
 This causes elevated levels of free copper in the blood,
which results in copper deposition in the brain,
particularly in the basal ganglia, in the Descemet’s
membrane in the cornea (Kayser–Fleischer rings only
seen on slit lamp examination of the eyes) and in the
liver, which causes cirrhosis.
 Patients typically present in their teens or early adult
life with atypical parkinsonism, tremor, dystonia,
cerebellar signs and cognitive decline.
 Patients can also present with prominent psychiatric
symptoms, including a personality change, emotional
lability and psychosis.
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27.  It is uncommon for neurological manifestations to
occur after the age of 40 years.
 The diagnosis is made by identifying low levels of
ceruloplasmin with high free copper in the urine and
serum after a penicillamine challenge.
 An MRI brain may show cortical atrophy or signal
change in the putamen and a liver biopsy can provide
a tissue diagnosis.
 Genetic testing is not practical due to the large
number of mutations that have been found.
 The disease is treated with copper-binding agents
such as penicillamine, trientine or tetrathiomolybdate
and the neurological damage may be partly
reversible. 27
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28. HUNTINGTON’S DISEASE
 Huntington’s disease (HD) is an autosomal
dominant disorder, presenting in adults usually
but occasionally in children.
 It is due to expansion of a trinucleotide CAG
repeat in the Huntingtingene on chromosome 4 .
 The disease frequently demonstrates the
phenomenon of anticipation, in which there is a
younger age at onset as the disease is passed
through generations, due to progressive
expansion of the repeat.
 The prevalence is about 4–8/100 000.
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29. HUNTINGTON’S DISEASE
 Clinical features
 HD typically presents with a progressive
behavioral disturbance, abnormal movements
(usually chorea), and cognitive impairment
leading to dementia.
 Onset under 18 years is rare but patients may
then present with parkinsonism rather than
chorea (the ‘Westphal variant’).
 There is always a family history, although this
may be concealed.
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30. HUNTINGTON’S DISEASE
 Investigations and management
 The diagnosis is confirmed by genetic testing;
pre-symptomatic testing for other family
members is available but must be preceded by
appropriate counselling .
 Brain imaging may show caudate atrophy but is
not a reliable test.
 There are a number of HD mimics.
 Management is symptomatic.
 The chorea may respond to neuroleptics such as
risperidone or sulpiride, or tetrabenazine.
 Depression and anxiety are common and may be
helped by medication.
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31. NEUROLEPTIC-INDUCED MOVEMENT DISORDERS
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32. NEUROLEPTIC-INDUCED
MOVEMENT DISORDERS
 Dopamine blocking drugs used to treat
psychiatric illness or as antiemetics or vestibular
sedatives can cause a variety of movement
disorders:
1. Acute dystonic reactions
2. Medication-induced parkinsonism
3. Akathisia
4. Tardive dyskinesia
5. Neuroleptic malignant syndrome
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33. ACUTE DYSTONIC REACTIONS
 Dystonia develops in 2–5% of patients on
neuroleptics or antiemetics (metoclopramide and
prochlorperazine).
 This reaction is unpredictable and can occur even
after single doses of the medication.
 The range of dystonias includes torticollis,
oculogyric crisis and trismus.
 They respond rapidly to intravenous injection of
an anticholinergic drug (e.g. procyclidine or
benztropine).
 Some patients on neuroleptics who develop these
reactions are also treated or cotreated with an
oral anticholinergic. 33
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34. AKATHISIA
 Akathisia is a restless, repetitive and irresistible
need to move, usually caused by neuroleptics.
 It may cease with mndrug withdrawal or be
treated with a benzodiazepine or propranolol
 Treatment aimed at the cause
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35. TARDIVE DYSKINESIA
 Tardive dyskinesia is a movement disorder that
develops after chronic exposure to neuroleptics.
 It can be irreversible and may worsen when the
offending medication is stopped.
 Involuntary movements affect the face, mouth and
tongue causing lip smacking, grimacing and dystonic
grimacing.
 It can be avoided by using newer atypicalneuroleptics.
 It is thought to be due to drug-induced
supersensitivity of the dopamine receptors.
 The evidenced-based guidelines of the American
Academy of Neurology recommend the use of
clonazepam and ginkgo biloba for TD
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36. NEUROLEPTIC MALIGNANT SYNDROME
 Occasionally, dopamine receptor blocking drugs
can cause this syndrome, which manifests with
 Extreme rigidity
 Fluctuating conscious level
 Fever
 Autonomic disturbance
 Elevated serum creatine kinase.
 The drug in question should be withdrawn and
the patient treated with a dopamine
agonist/levodopa and dantrolen (postsynaptic
muscle relaxant)
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37. RESTLESS LEGS SYNDROME
 This is a common syndrome that can be familial
or sporadic.
 It can be associated with
 Iron deficiency
 Anaemia
 Pregnancy
 Peripheral neuropathy
 Uremia .
 Hypothyroidism
 Parkinson disease
 Drugs (antidepressants, antipsychotics, lithium etc.)
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 Patients complain of an unpleasant sensation in
their legs and an irresistible urge to move their
legs, which is worst at night when they are
resting or inactive. Can cause sleep disturbances
 Often associated with depression and anxiety
 Symptoms are relieved by movement, and can be
treated with dopaminergic medication

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