Title: Familial Creutzfeldt-Jakob Disease with early onset myoclonus: A case for fulminant progression
Abstract: Dear Editor, Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressing neurodegenerative disease. It can be classified into sporadic (sCJD), familial (fCJD), variant (vCJD), and iatrogenic types (iCJD).[1] The largest cluster of fCJD is seen as an autosomal dominant trait in Israel in Jews of Libyan ancestry albeit rare in South East Asia.[2] The first kindred of fCJD with genetically proven D178N-129V haplotype reported from South-East Asia in 2019 presented with progressive forgetfulness, behavioral abnormality, ataxia, and lastly myoclonus.[3] Myoclonus presents as the early presenting symptom in only 0.5% of sCJD.[4] fCJD has a prevalence of 69–86% of myoclonic jerks in the later course of the disease but none of the cases of reported myoclonic jerks as the initial symptoms.[3] Here we report the first kindred of fCJD with early onset myoclonus from Southeast Asia with fulminant progression. A 54-years-old married male with a medical history suggestive of diabetes and hypertension was presented with myoclonic jerks which started two years back. This was followed by forgetfulness over the next two–three months. Forgetfulness was followed by loss of control over bladder and bowel functions over the next two months. The cognitive decline started almost simultaneously with the loss of bowel and bladder and rapidly deteriorated within eight months of the onset of myoclonic jerks. After one year of onset of symptoms, he gradually decreased speaking and started blurting out incoherent words for the last four months. The myoclonic jerk would last for less than a second with a fall on either side without any loss of consciousness occurring only in the morning within one hour of waking. There was a family history of forgetfulness and cognitive decline in his paternal grandmother, father, and sister, although we could not get a genetic examination/history of the same in the family. Examination revealed apraxia, dysphasia, shuffling gait, and pout reflex. Clinical examination revealed brief jerks lasting for 1–2 s with a fall on either side with intact consciousness. Mental status examination revealed severe cognitive decline with verbal and motor stereotypy. On MRI brain, there was global cortical atrophy scale grade 3, chronic white matter ischemic changes Fazeka score 3, hippocampal fissural cysts, bilateral symmetric hyperintensities in caudate nuclei, and partially empty sella. EEG was suggestive of bilaterally synchronous triphasic waves occurring periodically with periods of burst suppression suggestive of encephalopathy. The patient was diagnosed with probable CJD based on clinical features and investigations. He was started on Donepezil 10 mg and T. Memantine 20 mg, Sertraline 50 mg, Sodium valproate 400 mg, and Haloperidol 2 mg, daily, respectively, and given supportive care. However, he succumbed to his illness within 1 month of his index consultation. fCJD reportedly presents with early non-specific symptoms like headache, anxiety, and sleep disturbances followed by cognitive decline, cerebellar ataxia, myoclonus, and pyramidal and extrapyramidal deficits.[2] The median survival years after symptom onset is 7–50 months emphasizing the fulminant progression of the disease.[3] In CJD, myoclonus can be rhythmic or non-rhythmic occurring in the limbs or generalized with axial predominance and may cause dystonic posture and fall. It can also be unilateral and associated with apraxia. It can be induced by movement and external stimuli.[5] Few possible explanations can be proposed to explain the early presenting myoclonus in fCJD even though a detailed genetic study/CSF analysis could not be done in our patient due to lack of consent. The involvement of caudate nuclei and spongiform degeneration as evidenced by hippocampal fissural cysts as seen in our case may have led to early onset myoclonus and fulminant progression.[1,2] The early myoclonus can also be explained by the mutation of the prion protein itself.[6] This case highlights that fCJD should be considered in patients with early onset myoclonus in familial dementia. Consent for publication Written informed consent was obtained from the patient and her guardian for the publication of this case report. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.