Posted by Dr. Bijoykumar Barik on Thursday, 22nd July 2010Creutzfeldt-Jakob Disease (CJD) is a relatively rare cerebral disorder involving rapid decrease of mental function and movement known to be caused by abnormal brain proteins called “prions”. It is the most frequent human variety of prion diseases and similar to the various transmissible spongiform encephalopathies that afflict animals including the new variant “Mad Cow Disease” (nv CJD). Prions cause devastating changes in the CNS particularly the grey matter causing neuronal loss, gliosis and diffuse fine-meshed vacuolation of the neuron containing structures.
The yearly incidence is about 1 in a million. Creutzfeldt & Jakob in the early 1920’s described six cases of human progressive dementing illness with spasticity, ataxia and involuntary movements. Bjorn Sigurdsson termed slow infection in 1954 with reference to a chronic degenerative disease of brain in sheep known as scrapie. In 1957 Gajdusek and Zigas described the illness among the fore people of Eastern New Guinea practicing ritual cannibalism. In 1982 Prusiner coined the term “prion” to describe the unconventional pathogen.7 All prion disorders are associated with aberrant metabolism of PrP, the prion protein. However, in India the first case of CJD was reported in 1965 and since then sporadic cases have been reported very often.8
We report such a relatively rare case from western Orissa with great deal of diagnostic difficulties at the out set.
CASE REPORT :
S.B., a 68 year old female was admitted to a local hospital for failing memory and behavioral changes followed by lack of co-ordination and visual disturbances. She was provisionally diagnosed to be a case of Alzheimer’s Disease in early 2002. Gradually she noticed pronounced mental deterioration and involuntary movements and weakness of extremities with altered sensorium for which she was admitted to a central hospital and was treated on the line of cerebrovascular accident. On 12th February 2003 she was referred to V.S.S. Medical College, Burla for further treatment.
There was no past history of similar illness / phychiatric or neurological disorder. There was history of cataract operation with intraocular lens (IOL) implantation in August 2002. But there was no history of vaccination in the recent past. She was a newly detected diabetic and hypertensive but under control. She was married and blessed with two children, non-vegetarian by diet (no history of beef or pork intake) and no history of addiction of any kind. Family history was not suggestive.
ON EXAMINATION :
The patient was stuporus, non-communicative, feebly responsive to painful stimuli, pulse rate 86/pm, regular, BP 130/80mmHg, afebrile, per abdomen, CVS and respiratory system revealed no abnormality.
CNS examination revealed stiffness in all the limbs, deep tendon reflex increase, myoclonus present with flexor plantar response.
Routine investigations showed Hb-11.5gm%, MP (QBC)-negative, TLC-10000/mm3, ESR-15mm, FBS-86 mg%, Serum Na + 138, Serum K + 4.3, Blood urea – 67 mg%, Serum creatinine – 1.05 mg%. CSF, urine examination and ECG were within normal limit.
CT Scan (Fig.1) was normal. The EEG (Fig.2) revealed presence of periodic complexes at an interval of less than one/second arising from both sides, which was characteristic of C.J. disease.
She was initially treated on the line of metabolic encephalopathy. During follow up the patient developed generalized tonic clonic seizures next day of admission but was controlled with anti-epileptic medication. However, there was gradual deterioration of neurological status and she died on 22-02-03 after about 10 days of hospital stay.
Sporadic form of CJD is the most frequent variety presenting spontaneously, not transmitted from person to person.6 Familial form is transmitted as autosomal dominant inheritance in 15% cases due to a point mutation in the gene encoding PrP at codon 178 producing asparagine.3 Iatrogenic form results with corneal transplants, dural grafts, intracerebral EEG recordings and recipients of human growth hormone in growth failure cases, although the incidence after cataract operation and IOL implantation have not been reported.
The clinical tetrad of CJD is subacute progressive dementia, myoclonus, typical periodic complexes on the EEG and a normal CSF.7 The cognitive impairment may be quite global in nature as evidenced by neuropsychological testing. Prodromal symptom experienced in approximately 1/4th of patients may occur weeks to months preceding onset of progressive dementia, which is the hallmark of the illness.4 Ataxia seen in 1/3rd of patients initially but ultimately occur in as many as 70% cases. In about 10% of patients the illness begins with almost stroke – like suddenness and runs its course rapidly in a matter of few weeks or months.
Heidenhain’s variant of CJD includes cortical blindness and visual agnosia where as in Brownell and Oppenheimer variant cerebellar ataxia with a relative paucity of cognitive impairment (17%) dominates, Dyskinesias, prominent extrapyramidal features, seizure, LMN features, autonomic dysfunction, stroke-like presentations and supranuclear gaze palsies are some of the exceptional presentations.7 Jakob type of CJD is the cortio-striato-spinal variant where as the lesion in the diffuse variety (Stern and Garcin) lies in the basal ganglia and thalamus. Besides in the panencephalitic form there is involvement of white matter out of proportion to the degeneration of grey matter.4
Only the electro-encephalogram is of diagnostic significance amongst all routinely available laboratory studies. In well advanced disease 1-2 cycles per second triphasic sharp waves superimposed on a depressed background are characteristic. These periodic sharp waves are asymmetrical tend to become slower with progressive course of the disease. This is evident within 3 months of onset in approximately 80% cases. A non-specific abnormality in the form of symmetrical theta and delta waves on an irregularly depressed background may be seen before the occurrence of periodic sharp waves in about 50% cases. Often episodic burst suppression high voltage activity is seen which is less specific and rare during the early course.5
CFS parameters are usually normal and imaging studies of brain remain normal in majority of patients. Cerebral atrophy may be noted occasionally on MRI.1 Positron emission tomography (PET) in few cases shows regional hypometabolism of glucose reflecting loss of neuronal function. Brain biopsy specimen for neuropathologic study is the definitive diagnosis revealing a fine-meshed spongy vacuolation and should be carried out if thought by the physician with due consent by family members as the disease is invariably fatal. However, a finding of normal tissue morphology does not exclude the disease and in such situation typical EEG abnormality can lead to a correct diagnosis.2
As such caution should be maintained while operating for cataract and if any IOL is planned for the patient, the transmission of CJD should be kept in mind.
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3. Goldfarb LG, Petersen RB, Tabaton et al, Fatal familial insomnia and familial creutz feldt Jakob disease : Disease phenotype determined by DNA polymorphism. Science : 1992:258:806-8.
4. Kretzschmar HA : Human prion Diseases (Spongiform encephalopathies) Arch Virol supplementum : 1993; 7:261-293.
5. Levy SR, Chiappa KH, Burke CJ, Young RR. Early evolution and incidence of EEG abnormalities in CJD. J. Clinic. Neurophysiol. 1986; 3 : 1 – 21.
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7. Prusiner SB, Human Prion Diseases : Ann. Neurology, 1994a; 35:385-95.
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