CASE PRESETATION

Dr. Sana Fatima

PGR Neurology
PINS/LGH
BIO DATA
• Name : Qudrat Ullah
• Age : 11 years
• Address : Pakpattan
• DOA : 06.02.19
• MOA : OPD
• Source of history : Parents
PRESENTING COMPLAINTS

• Walking difficulty 6 months

• Behavioural changes 6months

• Speaking difficulty 2 months

HOPI

Patient was in usual state of health 6 months back when he

developed C/O inability to bend his left leg and walk with dragging
leg.
• gradual in onset
• progressive in nature
• Initially patient was able to bear his weight and walk with 1 person
support later he became bed bound over period of 4 months
• Now his functional status is that he is totally dependant on
attendands for his routine care.
He developed behavior issues for 6 months
• noticed by school teachers due to his lack of attention
• poor progress in class
• irrelevant and aggressive behavior
• inappropriate smile and weeping spells.
After 4 months of initial symptoms patient developed speaking
difficulty
• initially slurring of speech but meaningful words
• Later utter words which can not be understood
• There was no history of fever, headache, vomiting , fits.

• No history of abdominal pain, vomiting, yellowish discolouration of

body at birth & early life.

• No urinary or bowel complaints.

SYSTEMIC HISTORY
• Unremarkable
GENERAL HISTORY
• No Loss of appetite
• No weight loss
PAST HISTORY
• Medical & surgical history : not significant
PERSONAL HISTORY
• Birth by SVD
• No H/O delayed milestones
• Student of 5th class, left school for 5months due to current illness.
• Non addict , non smoker
FAMILY HISTORY
• Six siblings , 3 elder sisters and 2 younger sisters
• 1 elder sister died at age of 8 years (aggressive behavior , ascites, no
further information )
• Parents have non consangineous marriage.
DRUG HISTORY
• Tab Baclin 10 mg 1 x BD
• Tab Rivotril 0.5 mg x ½ H.S
• Tab Kemadrin 5mg 1 x BD
• Tab movax 2 mg 1x BD
EXAMINATION
• A thin lean boy having a vacuous smile lying in bed conscious,
relatively slow in following commands and not fully cooperative for
examination with vitals
• BP: 110/70 mmHg
• PULSE: 80/min
• TEMP: afebrile
• RR: 18/min
• GPE : pallor positive, yellowish sclera , rest is unremarkable.
CNS
GCS: E4 M6 V3=13/15
HMF
• Conscious level : fully conscious
• Not oriented in time, place and person.
• Memory : can,t be assessed
SPEECH
• Non comprehensive & Non fluent .
• Repetition, nomination, calculation,reading & writing could’nt be
assessed.
• Pupils: Reactive to light ,B/L golden brown rings at periphery of
cornea.

• Fundus: normal

• CRANIAL NERVES: limited examination , appears to be intact

Upper limbs
Right Left

Bulk decreased decreased

Tone Normal Normal

Power Can’t be assessed Can’t be assessed

Reflexes Absent Absent

Lower limbs
Right Left
Bulk Decreased decreased
Tone Slightly increased Markedly increased
Power Can’t be assessed Can’t be assessed
Reflexes Absent Absent
Planters Down going Downgoing
• Cerebellum : limited examination, intact.

• Gait and sensory system : could not be assessed.

SYSTEMIC SYSTEM

• GIT : spleen palpable 3 fingers below costal margin, liver not palpable,
BS +ive

• Rest of the systemic examination was is unremarkable.

DIFFERENTIALS
• Deposition disorders
• Westphal variant of HD
• Juvenile Parkinson,s Disease
• Post encaphilitic sequelae
INVESTIGATIONS
• CBC: hb.9.8, tlc 4.2, plt 98000
• LFTS: ALT 24, AST 28, ALP 475
• PT/APTT/INR: 2.2
• RFTS:UREA 37, Cr 0.8
• S/E:Na 144, K4.5 ,Ca 9.5
• Serum ceruloplasmin: 4 mg/dl.
• USG ABDOMEN:
LIVER :11.5 cm ,early coarse texture , regular margins, no focal
leions
spleen : enlarged.

• SLIT LAMP EXAMINATION: B/L KF rings

MRI BRAIN PLAIN
T1 T2
FLAIR
PROVISIONAL DIAGNOSIS

• Wilson’s disease
INTRODUCTION
• Wilson’s disease is an autosomal recessive inherited disorder in which
defective biliary excretion of copper leads to its accumulation,
particularly in liver and brain.
• Wilson’s disease is due to mutations of the ATP7B gene on
chromosome 13, which encodes a copper-transporting P-type ATPase
(ATP7B) residing in the trans-Golgi network of hepatocytes.
EPIDEMIOLOGY
• The prevalence of Wilson’s disease is 1 per 30,000 individuals
• Fulminant presentation is more common in females than in males
• Wilson’s disease may present symptomatically at any age, although
the majority presents between ages 5 and 35
CLINICAL PRESENTATION
HEPATIC DYSFUNCTION :
• Presenting feature in more than half of patients, 3 major patterns of
hepatic involvement are:
• Chronic active hepatitis
• Cirrhosis
• Fulminant hepatic failure…
Neuropsychiatric features:
• Most common presenting feature is tremor which is predominantly
resting..
• Frequent early symptoms include:
• Difficulty speaking
• Excessive salivation
• Ataxia
• Masklike facies
• Clumsiness with hands
• Personality changes
LATE MANIFESTATIONS:
• Emotional lability
• Disinhibition
• Self injurious behaviour

MUSCULOSKELETAL MANIFESTATIONS:
• Arthropathy of wilson generally is degenerative process that resemble
premature osteoarthritis.
• Involves spine and large joints.
HEMATOLOGICAL AND RENAL
MANIFESTATIONS:
• Coomb’s negative acute intravascular hemolysis
• Urolithiasis
• Hematuria
KAYSER-FLEISCHER RINGS:
• Formed by deposition of copper in descemet membrane of cornea
• Color may range from greenish gold to brown
• Observed in almost 90% of individuals with Wilson’s disease
Additional manifestations
• Skeletal abnormalities like osteoporosis, osteomalacia ,spontaneous
fractures
• Cardiac rhythm abnormalities
• Skin pigmentation
• Bluish discoloration of nails
DIAGNOSTIC CRITERION
• Leipzig criterion
KF.Rings
MRI features
MANAGEMENT:
• Mainstay of therapy is lifelong use of chelating agents
• Symptoms may worsen with initiation of chelation
• TIPS is reserved for recurrent variceal bleeding
• Liver transplantation is curative
• Patients should generally avoid eating foods with high copper content
such as organ meat ,chocolates nuts mushrooms legumes and shell
fish
D-Penicillamine
• The major effect of D-penicillamine in Wilson’s disease is to promote
the urinary excretion of copper.
• The maintenance dose is usually 750–1500 mg/day administered in
two or three divided doses.
• Dosing in children is 20 mg/kg/day
• D-Penicillamine is best administered 1 h prior to meals, because food
inhibits its absorption.
• Since D-penicillamine tends to interfere with pyridoxine action,
supplemental pyridoxine should be provided (25–50 mg/day).
Monitoring of treatment
• Adequacy of treatment can be monitored by measuring 24-hour
urinary copper excretion while on treatment. This is highest
immediately after starting treatment and may exceed 16 micromol
(1000 microg) per 24 h at that time.
• For long-term treatment, most important sign of efficacy is a
maintained clinical and laboratory improvement.
• Urinary copper excretion should run in the vicinity of 3–8 micromol
per 24 h on treatment
• D-penicillamine is rapidly absorbed from the gastrointestinal tract. If
it is taken with a meal, its absorption is decreased overall by about
50%.
• Once absorbed, 80% of it circulates bound to plasma proteins.
Greater than 80% of excretion is via the kidneys.

• The excretion half-life of D-penicillamine is on the order of 1.7–7 h.

• Tolerability of Dpenicillamine may be enhanced by starting with
incremental doses, 125–250 mg/day increased by 250 mg increments
every 4–7 days to a maximum of 1000–1500 mg/day in 2–4 divided
dosages. Administration of doses 1500 mg per day or higher at once
may lead to rapid and often irreversible neurological deterioration.

• Rapid re-administration of the treatment in patients who stopped it

for longer time may also evoke irreversible neurological signs.
• D-penicillamine is associated with numerous side effects.
• Early sensitivity reactions marked by fever and cutaneous eruptions,
lymphadenopathy, neutropenia or thrombocytopenia, and
proteinuria may occur during the first 1–3 weeks.
• Significant bone marrow toxicity includes severe thrombocytopenia
or total aplasia. In these conditions, D-penicillamine should be
discontinued immediately.

• Late reactions include nephrotoxicity, usually heralded by proteinuria

for which discontinuation of drug should be immediate.
Trientine
• Trientine (triethylene tetramine dihydrochloride) was introduced in
1969 as an alternative to D-penicillamine.
• Trientine is a chelator and like D-penicillamine, trientine promotes
urinary copper excretion.
• Typical dosages of trientine are 900–2700 mg/day in two or three
divided doses, with 900–1500 mg/day used for maintenance therapy.
• In children, dose generally used is 20 mg/kg/day given in two or three
divided doses.
• Trientine should be administered 1 h before or 3 h after meals..
Ammonium tetrathiomolybdate
• Ammonium tetrathiomolybdate (TM) is a very strong decoppering
agent.
• TM complexes with copper; in the intestinal tract it prevents
absorption, and in the circulation renders copper unavailable for
cellular uptake
• TM remains an experimental therapy, and it is not commercially
available. As yet, clinical experience with this drug is limited.
ZINC
• Zinc interferes with the uptake of copper from the gastrointestinal
tract.
• Different zinc salts (sulphate, acetate, gluconate) are used.
• The recommended dose is 150 mg elemental zinc/day, administered
in three divided doses, 30 min before meals.
VITAMIN E:
• Antioxidants, mainly vitamin E, may have a role as adjunctive
treatment .
• Serum and hepatic vitamin E levels have been found to be low in
Wilson’s disease
• Symptomatic improvement when vitamin E was added to the
treatment regimen has been occasionally reported but no rigorous
studies have been conducted
• Family screening
• Chelation therapy before onset of neurologic signs can prevent
neurologic deterioration.