DEGENERATIVE DISEASE OF THE BRAIN 10/14/20151Dr. Alka Stoelinga

DEGENERATIVE DISEASE OF THE BRAIN

04/19/23 1Dr. Alka Stoelinga

PARKINSON’S DISEASE• Parkinsonism is a chronic and progressive clinical syndrome

resulting from deficiency of the neurotransmitter dopamine as a consequence of degenerative, vascular, or inflammatory changes in basal ganglia.

• Parkinsonism is characterized– Bradykinesia– Rigidity– Instability (Postural)– Tremor at rest/ resting tremor

• (Mr. Parkinson is a fine BRITish gentleman)• Parkinson’s disease-

– Incidence 1 to 2 per 1000 , 2 per 100 among people older than 65 years

– Sex incidence –Equal, – Less in cigarette smoker.


Etiology:• Idiopathic

– Also called Paralysis agitans or Parkinson's disease Poisoning

MPTP(Methyl-phenyl Tetrahydropyridine) causes severe parkinsonism CO Cyanide Manganese

• Drugs: Neuroleptics

Haloperidol, Chlorpromazine Antiemetics

Metoclopramide Reserpine , alpha-methyldopa• Structural lesions around basal ganglia:

– Trauma/ Tumor/ Abscess/ Infarct• Postencephalitic Parkinsonism


• Pathology – Loss of pigmented dopaminergic neurons in

substantia nigra– Progressive cell degeneration in substantia nigra– Presence of neuronal eosinophilic inclusion bodies

i.e., Lewy bodies– Atrophic changes– Reduction of dopaminergic output from substantia

nigra to the globus pallidus resulting in inhibition of activation of cerebral cortex causing Bradykinesia.


Positive Alpha-Synuclein staining of a Lewy body in a patient with Parkinson's disease

PD is considered a synucleinopathy due to its abnormal accumulation of the alpha- synuclein protein in the brain in the form of lewy bodies as opposed to other diseases such as Alzheimer's disease where the brain accumulates tau protein in the form of neurofibrillary tangles.

04/19/23 Dr. Alka Stoelinga 5


Parkinson’s disease


Clinical features– Classical features consists of :

• Bradykinesia (Slow movements, mask facies, reduction of automatic movements)

• Rigidity (Cogwheel)• Instability (Postural)• Tremor (Resting).

– Other nonspecific features are : • Tiredness, muscle aches, mental slowness, depression, Change in the hand

writing may be the only features at early stage– In an advanced disease:

• Tremor-coarse ,pin-rolling, resting as well as intentional tremor• Mask like face• Bradykinesia• Flexed posture• Gait –slow walking, shortened stride, reduced arm swing(Shuffling

gait), tendency to run (festination gait), reduced arm swing, Impaired balance on turning

• Glabellar tapping: Sustained blinking of eyes (Positive Myerson’s sign).

• Speech: Soft, rapid, indistinct• Later stage: Impairment of intellectual function




Parkinson’s disease


Differential diagnosis:• Hypothyroidism• Depression• Drug induced parkinsonism• Multi infarct dementia• Alzheimer’s disease• Essential benign familial tremor• Wilson’s disease• Huntington’s disease• Corical basal ganglionic degeneration04/19/23 12Dr. Alka Stoelinga

Diagnosis:Medical history and neurological examination


Investigations• No specific investigations which can help diagnosis• Gold standard- Lewy bodies during autopsy • 3 Criteria required

– First: Requires the person to suffer from slowness of movement (Bradykinesia) and either rigidity, rest tremor or postural instability.

– Second: other possible causes for symptoms have to be ruled out– Third: The person would have to have 3 or more of the following during onset

or evolution:• Unilateral onset• Rest tremor,• Progression• Asymmetry of motor symptoms• Response to levodopa during at least 5 years• Clinical course of at least ten years and • Appearance of dyskinesias induced by the intake of excessive levodopa.• Accuracy of diagnostic criteria evaluated at autopsy is between 75 and

90%


• PET scan shows decreased dopamine activity in the basal ganglia


Management:• Treatment of parkinsonism is directed toward

restoring the dopaminergic and cholinergic balance in the striatum by blocking the effect of Acetylcholine with Anticholinergics or by enhancing dopaminergic transmission.


Management • Levodopa :– It is converted into dopamine after decarboxylation and thus

replaces the dopamine deficiency in brain.– Start with 50 mg 8 hourly, and gradually increase the dose– S/E: Postural hypotension, nausea, vomiting, dystonias,

hallucination, delusion are important side effects– To prevent the side effects or reduce the dose it is usually

combined with Carbidopa or Benserazide. • Levodopa250mg+Carbidopa 25mg• Levodopa 250mg+ Banserazide 50mg– Late deterioration occurs in the form of wearing off effect

( end of dose) and on –off phenomenon


• Decarboxylase inhibitors (Carbidopa and Benserazide) :• Reduce side-effects by reducing peripheral conversion of

levodopa to dopamine • Anticholinergic (Trihexyphenidyl/Benztropine) • Young patients with less bradykinesia• Reduces the over activity of acetylcholine in negrostriatal

pathway.• Reduce tremor and rigidity.• ADR: Dry mouth, Blurred vision, urinary retention, confusion • Amantadine :• Rx of choice in age >60• Enhances the release of dopamine at the nerve terminal. • Can be use in early disease.• Useful in Bradykinesia• Started early in the course.


• Dopamine receptor agonists (Bromocriptine, Pergolide, Cabergoline)

• Act directly on striatal receptors.• Monoamine oxidase type B (MAO-B) inhibitor

(selegiline) • Increases the availability of neuronal dopamine by

reducing its metabolism.• Associated with many adverse effects.• Only drug in Parkinsonism that is thought to arrest the

progression of disease• Catechol-O-methyl-transferase (COMT) inhibitor

Entacapone :• Prolongs the availability of dopamine by inhibiting the

metabolism of dopamine and levodopa outside the neuron.


• Surgery – Stereotactic thalamotomy– Fetal midbrain cells implantation (experimental)

• Physiotherapy and speech therapy • Prognosis :– complications of immobility and tendency to fall


HUNTINGTON’S DISEASE• Genetic degenerative brain disorder• Disease starts in adult life• Demonstrates “anticipation”: Younger age of onset

in subsequent generation• Characterized by presence of HD gene located on

chromosome 4p.• CAG trinucleotide repeat expansions that codes for

protein called huntingtin.• HD mutation leads to abnormal cleavage of

huntingtin protein interferes nuclear mechanism cellular death.

• Inherited in Autosomal dominant fashion



Clinical features:• Starts in middle adult life• Progressively worsening chorea• Psychiatric symptoms• Dementia (Memory is preserved till later

stages Lack of judgement, disinhibition, inattention associated with depression)

• Poorly coordinated gait• Seizures• In juvenile variety: Parkinson like features


Clinical Hallmark

• Chorea (Fidgeting sudden movement of limbs or trunk)

• Behavioral disturbances


Diagnosis:• Ct scan/MRI head• DNA analysis- DNA repeat expansionsManagement:• No specific management• Symptomatic management• Treatment of chorea: Tetrabenazine• Genetic counseling


ALZHEIMER’S DISEASE• Most common cause of dementia• Seen in patients >45 years• 5% of population >65years suffer from dementiaEtiology:• Genetic• Atrophy:Cerebral cortex and Hippocampus• HPE: Senile plaque,neurofibrillary tangles• Neurotransmitter abnormality especially cholinergic

neurotransmitters


Clinical features:• Memory: Delayed recall• Short term memory more impaired• Apraxia: Characterized by loss of the ability to

execute/carry out learned purposeful movements, despite having the desire and the physical ability to perform the movements.

• Aphasia• Anosognosia: Denial of anything wrong• Acute worsening by Intercurrent illness• Depression04/19/23 27Dr. Alka Stoelinga

Investigation:• CT/MRI head• EEG• Blood: CBC, ESR, Thyroid function test, ANA,

Anti ds DNA,VDRLManagement:• No definitive treatment• Cerebral cholinesterase inhibitors: Donepezil,

Rivastigmine• Supportive treatment


PICK’S DEMENTIA:• Degeneration of frontal and temporal lobes• Picks bodies in HPE• Dementia,AphasiaLEWY BODY DEMENTIA:• Similar to parkinson’s disease:Lewy bodies are

found in cerebral cortex• Dementia,parkinson’s like features


PRION DISEASE/CREUTZTELDT JAKOB DISEASE(CJD):

• Due to prion:Infectious proteins• Can be sporadic/Genetic/Acquired• Characterized by progressive

dementia,myoclonus and characteristic EEG• Variant of CJD: seen in UK: Mad cow diseaseKuru diseae:Another disease


BELL’S PALSY• This is common,acute,isolated facial nerve

paralysis• Infection results in swelling of the nerve

within the facial canal in the petrous bone.• Swelling is responsible for initial loss of nerve

impulse conduction leading to facial paralysis.Causes: • Idiopathic• Due to reactive latent HSV-1,LMN


Clinical feature:Symptoms:• Onset: Subacute,within few hours• Preceded by pain around the ear• Weakness or inability to move on one side of face• Numbness(without objective loss of sensation)• Hyperacusis• Loss of tear• Impairment of taste on the anterior 2/3rd of the

tongue• Dribbling of saliva and water from the affected side• Collection of food in the mouth on paralyzed side04/19/23 32Dr. Alka Stoelinga

Signs:• Loss of wrinkling on the affected half of

forehead• Inability to close the eye• Bell’s Phenomenon: Upward rotation of the

eyeball on trying to close the affected eye• Flattening of the nasolabial fold• Loss of retraction of the angle of the mouth,

while showing his teeth


Bell’s palsy


Bell’s Palsy


Management:Investigation: EMG Mean action potential decreasedTreatment:• No proven treatment• Steroid: Prednisolone 60mg/d for 1 week It reduce edema of the facial nerve,and may limit damage and

speed recovery• Acyclovir• Both combined: Acyclovir+Prednisolone=More effective• Supportive treatment: Artificial tear drop Eye pad04/19/23 36Dr. Alka Stoelinga

Prognosis:• Spontaneous recovery seen in 70-80% within

2-12 weeksPoor prognostic factors:Severe pain at onsetComplete palsy at onsetElderly patientDecreased MAP after 1 week on EMG


RAMSAY HUNT SYNDROME

• Herpes zoster of geniculate ganglion causes facial palsy with herpetic vesicles in the external auditory meatus,this combination is called Ramsay hunt syndrome.


TRIGEMINAL NEURALGIA• It is a neuropathic disorder of one or both of the facial

trigeminal nerves. • It causes episodes of intense pain in any or all of the following: the

ear, eye, lips, nose, scalp, forehead, teeth or jaw on one side of the face.

• Exclusively seen in middle aged or elderly• Severe pain– for few seconds which occurs in paroxysms• TN brings about stabbing, mind-numbing, electric shock-like pain

from just a finger's glance of the cheek or spontaneously without any stimulation by the patient.

• Pain is brought on by stimulation of specific trigger zone in the face during: Washing,shaving,eating,talking,touching and cold wind may be the stimuli

• Cause: Occasionally due to Herpes zoaster


http://en.wikipedia.org/wiki/Neuropathy

http://en.wikipedia.org/wiki/Trigeminal_nerves

http://en.wikipedia.org/wiki/Pain

Management:• Exclude other causes• Medical therapy:1.Carbamazepine2.Phenytoin3.Injection of trigeminal ganglion with alcohol

or Phenol is a common procedure.4.Radiofrequency thermal rhizotomy of

trigeminal ganglion5.Microvascular decompression in facial canal04/19/23 40Dr. Alka Stoelinga

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DEGENERATIVE DISEASE OF THE BRAIN 10/14/20151Dr. Alka Stoelinga