Case 1
Mrs B, a 70-year-old married woman, was referred by her general practitioner to the local Old Age Psychiatry service, with a three-month history of progressive short term memory loss, mental slowing, and difficulties with activities of daily living (driving, shopping, writing letters). Her medical history showed no vascular risk factors. Her mother had had a history of dementia and died in her eighties. She worked in education prior to retirement, was married for 40 years and had two children. She was a nonsmoker, drank 1–2 units/week, and enjoyed gardening and walking.
Apart from increasing tiredness, there were no other symptoms suggestive of depression. She scored 79/100 on Addenbrooke's Cognitive Examination (ACE-R) (Mioshi et al., Reference Mioshi2006) and had a Mini-Mental State Examination (MMSE) score of 27/30 (Folstein et al., Reference Folstein, Folstein and McHugh1975). She was slow in tasks and had impairments in attention, memory, fluency, and visuospatial abilities.
When seen six weeks later, there had been decline in various domains; memory had worsened, speech had become less spontaneous, balance was poor, and she had begun to veer to the left. In addition, her handwriting and visuospatial abilities had further deteriorated. Neurological signs included an ataxic gait, dressing dyspraxia, left pronator drift, and dysdiadochokinesia. There was increased tone in the left upper limb. She had stopped her usual hobbies and described herself as “a rudderless ship.”
Routine blood tests were normal. The MRI scan showed asymmetric diffuse cortical high signal around the right hemisphere and the deep gray matter nuclei, particularly the caudate head and lentiform nucleus. This was most pronounced on diffusion-weighted imaging (DWI). No regional atrophy or white matter changes were seen. The patient was referred urgently to a neurologist. An autoantibody screen and tumor markers were all normal. The cerebral spinal fluid (CSF) total protein, glucose, and microbiology were normal and oligoclonal bands were negative. The CSF 14-3-3 and S100b proteins were raised, suggestive of sCJD. The electroencephalogram (EEG) showed right-sided sharpened theta and delta waves with poorly formed background activity, suggestive of an organic pathology. The classic triphasic pattern was not observed. The case was reported to the National CJD Surveillance team, based in Edinburgh (www.cjd.ed.ac).
Over the subsequent nine months, there was rapid decline in memory and mobility, loss of meaningful speech, and the development of primitive reflexes. Myoclonic jerks developed that responded to low-dose clonazepam. Home nursing care became necessary. She was admitted to the local hospice following two episodes of aspiration, where she passed away surrounded by her family.
Case 2
Mr C, a 69-year-old man, was admitted to a medical ward, with a 6–8 week history of forgetfulness, ataxia, dizziness, lethargy, reduced right-sided hearing, visual hallucinations, speech problems, and aggression. Prior to this admission, there was a 12-month history of deteriorating memory, feeling “depressed,” irritability, increased appetite, swallowing difficulties, “buzzing” noise inside his head, ataxia, personality change, and slurred speech.
Past medical history revealed hypothyroidism and hypertension. There was no family history of dementia. He was a retired engineer and lived with his partner. He had a supportive family. He was drinking approximately 4–5 bottles of wine/week. A neurological examination revealed reduced vision in the right eye, right-sided homonymous hemianopia, impairment in eighth cranial nerve function, poor coordination on finger-nose testing, and Romberg's test was positive.
Computed tomography (CT) and MRI brain scans were normal, as were the results of lumbar puncture (LP). He was given a diagnosis of Pick's disease and discharged home with memory clinic follow-up. A psychiatric opinion was not requested during this admission.
In subsequent weeks, Mr C deteriorated further and was re-admitted to the medical ward with confusion, expressive language problems, and inappropriate behavior mimicking “frontal lobe” syndrome (for example, over-eating, sexual disinhibition, laughing inappropriately, and intermittent aggression). He had developed myoclonic jerks involving the upper limbs and neck. Neurology opinion was sought at this stage. Repeat MRI scans showed increased signal in the caudate and thalamus, enhanced on DWI. There was mild global atrophy with small vessel disease changes. The case was reported to the National CJD Surveillance Team. He had an EEG which was compatible with either Pick's disease or CJD. CSF was sent for protein 14–3-3 and was suggestive of probable sCJD. The Liaison Psychiatry team was involved to help manage difficult behavior and psychological symptoms. The Palliative Care team was involved as he was unable to converse, his myoclonic jerks were progressive, he was choking on food, had developed aspiration pneumonia, and became bedbound. The family, following a discussion with the treating team, agreed to a Do-Not-Attempt-Resuscitation (DNAR) order and post-mortem examination of the brain. Within a few days he passed away peacefully on the medical ward. The post-mortem examination confirmed sCJD.
Discussion
Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common form of spongiform encephalopathy. The mean age of onset is around 65 years of age with a median survival time of four months. The spontaneous conformational change of prion protein to an infectious form, leading to abnormal prion aggregates, and neuronal damage is thought to be the pathology of the disease.
In sCJD a variety of psychological and behavioral symptoms occur, such as changes in personality, insomnia, depression, behavior dyscontrol, and psychosis, and can precede neurological involvement (Wall et al., Reference Wall2005). Cognitive impairment and ataxia often appear before myoclonic jerks, pyramidal, and extra-pyramidal symptoms. Rare presentations like occipital blindness, stroke-like onset, and pure cerebellar syndrome have also been reported (Henry et al., Reference Henry2002). Relentless deterioration, whatever the initial presentation, leads to death within months.
The clinical differential diagnosis of sCJD includes other rapidly progressive dementias (RPD), for example other forms of CJDs (variant, hereditary, or iatrogenic), para-neoplastic diseases like limbic encephalopathy (LE) and voltage gated potassium channel associated encephalopathy (VGKC-E). Hashimoto encephalopathy (HE) also runs a subacute course. In view of behavioral and psychological symptoms, chronic dementias like fronto-temporal dementia (FTD) and dementia with Lewy bodies (DLB) can be mistaken for sCJD (Rosenbloom and Atri, Reference Rosenbloom and Atri2011). Inflammation (acute or chronic), stroke, and hemorrhage should also be considered in the evaluation.
A definite diagnosis of sCJD requires a good clinical and corroborative history, neurological examination, neuro-imaging, and CSF examination, failing which a brain biopsy may be indicated to establish the etiology (Rosenbloom and Atri, Reference Rosenbloom and Atri2011). A comprehensive history focusing on the chronology of onset and nature of symptoms and trigger factors is valuable. In addition to a neurological examination, formal neurological testing provides information on memory, executive function, language, and visuo-spatial functions.
MRI scans in 79% of cases show high intensities in the caudate and putamen, prominent in FLAIR (fluid-attenuated inversion recovery) and DWI (Young et al., Reference Young2005). On EEG, in 60%–70% cases of sCJD, characteristic appearance of 0.5–2 Hz generalized bi- and triphasic waves are seen. In CSF examination, standard parameters (cell count, barrier function, and inflammatory reactions) are generally normal. The detection of protein 14-3-3 is a highly sensitive and specific marker for sCJD (Lemstra et al., Reference Lemstra2000). Other CSF brain proteins such as neuron-specific enolase (NSE), S-100 protein and tau protein are also found in high quantities in sCJD (Aksamit et al., Reference Aksamit, Preissner and Homburger2001).
There are at present no treatments to cure or delay the progression of the disease. Invariably patients present with both mental and physical health problems, and this poses the challenge of where best to manage them – on a medical or psychiatric ward, in palliative care facilities, residential care, or at home. In light of unusual presentation, patients may fall between the services and their families often get short shrift, especially when the behavior is challenging. Ideally, support from psychiatrists, neurologists, and physicians should be helpful irrespective of where they are admitted. Management is guided by general principles of symptomatic relief.
Psychiatrists can provide valuable input with regard to service provision, adequate diagnosis, advice on treatment, and management in a liaison psychiatry setting. Psychiatrists can advise on treatment of aggression, agitation, and restlessness with small doses of benzodiazepines or antipsychotics such as risperidone (Butler and Fleminger, Reference Butler and Fleminger2001). Antidepressants might be effective for depression or anxiety symptoms. Clonazepam and sodium valproate are used for myoclonus with some benefit.
Psychiatrists have to be involved in supporting relatives, advising on placements, capacity assessments and end-of-life issues. The National CJD Surveillance Team provides advice to local services, information for carers and details of other support agencies.
Conflict of interest
None.
