An autopsy case of MV2K-type sporadic Creutzfeldt-Jakob disease presenting with characteristic clinical, radiological, and neuropathological findings.

In Japan, because MV2-type sporadic Creutzfeldt-Jakob disease (CJD) is rare, little is known about its clinical and neuropathological characteristics. An autopsy case of MV2K-type sporadic CJD is presented, and the characteristic clinical, radiological, and neuropathological findings are discussed. The patient was a Japanese woman who died at the age of 72 years. Her initial symptom was rapidly progressive dementia. She then developed truncal ataxia and delusions. Approximately nine months after onset, she exhibited akinetic mutism. The total clinical course was 11 months. Magnetic resonance imaging revealed hyperintensity areas in the basal ganglia, thalamus, and hippocampus on diffusion-weighted images. In the cerebral cortex, this finding was slight and inconspicuous. Electroencephalography revealed no periodic sharp wave complexes. Prion protein (PrP) gene analysis revealed no mutations, and polymorphic codon 129 exhibited methionine and valine heterozygosity. In the cerebrospinal fluid, levels of both total tau and 14-3-3 proteins were elevated. Grossly, the brain weighed 1050 g before fixation and exhibited diffuse cortical atrophy. On histopathological examination, extensive fine vacuole-type spongiform degeneration was noted in the cerebral cortex. Numerous kuru plaques were observed in the cerebellum. PrP immunohistochemistry revealed extensive diffuse synaptic- and perineuronal-type PrP deposits in the cerebral cortex. Kuru plaques were strongly immunoreactive for PrP. Western blot analysis of brain tissue samples revealed mixed type 2 and intermediate type. Systematic and comprehensive investigations of both clinical and neuropathological aspects are required for accurate diagnosis.

[A case of genetic Creutzfeldt-Jakob disease that required differential diagnosis of acute encephalopathy associated with Sjogren's syndrome].

An 86-year-old female was admitted to our hospital with acute progressive gait disturbance and cognitive impairment. Brain MR diffusion weighted imaging revealed abnormal high signal intensities in the bilateral hemispheres, dominantly in the frontal lobe. We first suspected acute encephalopathy due to Creutzfeldt-Jakob disease (CJD) from her clinical information. At the same time, we could not negate the possibility of Sjögren's syndrome (SjS) -related encephalopathy based on the abnormal findings on brain MRI and positive anti-SS-A antibody in the serum. After consulting with an otorhinolaryngologist and a pathologist, biopsy of the salivary gland was performed with a strict precaution against infection of prion virus. Pathological examination of the biopsy specimen showed accumulation of many lymphocytes around the gland, which satisfied grade 4 in the Greenspan classification. A definite diagnosis of SjS was made based on the pathological findings, and intravenous high dose methylprednisolone followed by oral prednisolone were administered for suspected SjS-related encephalopathy. However, the neurological symptoms did not improve and we judged that SjS-related encephalopathy was unlikely. The poor response to steroid therapy and the presence of tau protein, strongly positive 14-3-3 protein and a codon 180: Val/Ile mutation in the cerebrospinal fluid finally led to a clinical diagnosis of genetic CJD. In-hospital cooperation in terms of infection prevention is important when performing invasive procedure in the case of suspected CJD to distinguish treatable encephalopathy.

Hepatic Encephalopathy Mimicking Creutzfeldt-Jakob Disease on Laboratory, Physiological, and Imaging Evaluations.

BACKGROUND Creutzfeldt-Jakob disease (CJD) is an irreversible, neurodegenerative, prion disease presenting with cognitive, behavioral, and motor dysfunction. The clinical presentations or laboratory findings of treatable autoimmune and metabolic processes may mimic those of CJD. Hepatic encephalopathy (HE) is a complication of severe hepatic failure that is characterized by neuropsychiatric manifestations. A case of HE whose laboratory, physiological, and imaging results were similar to that of Creutzfeldt-Jakob disease (CJD) in the process of treatment for HE is presented. CASE REPORT An 84-year-old woman with hepatic encephalopathy (HE) was admitted to our hospital because of acute consciousness disturbance. She had chronic hepatitis type C, liver cirrhosis, and hepatocellular carcinoma, and had had an episode of HE once. Her severe consciousness disturbance did not improve after treatment for concurrent hyperammonemia, unlike in her previous episode. Diffusion-weighted brain magnetic resonance imaging (MRI) showed widespread hyperintensity of the whole cortex. Her electroencephalogram showed periodic sharp wave complexes (PSWCs). Both total t-tau and 14-3-3 proteins were detected in her cerebrospinal fluid. According to these clinical data, CJD was highly suspected. However, the consciousness disturbance was alleviated by the tenth day of admission, and her general condition was markedly improved, which supported the initial diagnosis of HE. CONCLUSIONS The present results suggest that treatable disorders, such as HE, should be considered before making a final diagnosis of a fatal disease such as CJD, since the spectrum of diseases that CJD mimics is vast. We should also aggressively treat patients with severe conditions from which recovery is possible.

Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow. SUBJECTS AND METHODS: This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method. RESULTS: When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3. CONCLUSIONS: Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.

An autopsy case of Balamuthia mandrillaris amoebic encephalitis, a rare emerging infectious disease, with a brief review of the cases reported in Japan.

Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10-60 µm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.

Marchiafava-Bignami disease with hyperintensity on late diffusion-weighted imaging.

A 69-year-old man with a decades-long history of chronic alcohol consumption was admitted with gait disturbance (short steps and spasticity), deterioration of activity, and stuporous consciousness. Head magnetic resonance imaging (MRI) revealed hyperintensity on fluid-attenuated inversion recovery imaging in the corpus callosum and frontal white matter. The lesion later became more apparent on diffusion-weighted imaging. The clinical diagnosis was Marchiafava-Bignami disease (MBD). As temporary treatment, refraining from alcohol consumption and administration of vitamins were prescribed. The condition of the patient gradually improved. The purposes of this study were to demonstrate the clinical and radiological variety of MBD and to identify practical methods of treatment of this pathology.

Concomitant alpha-synuclein pathology in an autopsy case of amyotrophic lateral sclerosis presenting with orthostatic hypotension and cardiac arrests.

A 74-year-old man gradually developed muscular weakness in the upper extremities, followed by dyspnea and dysarthria over a 6-month period. He was admitted to our facility and diagnosed as having amyotrophic lateral sclerosis (ALS) based on clinical and neurophysiological findings. Two months later, transtracheal positive pressure ventilation (TPPV) was started. During his clinical course, orthostatic hypotension occurred a few times. He also had two episodes of transient cardiac arrest, and he died 15 months after disease onset. At autopsy, the brain, weighing 850 g, showed diffuse cortical atrophy, preferentially involving the frontal lobes. Microscopic findings included severe loss of neurons in the motor cortex, the motor nuclei of the brainstem and the anterior horns of the spinal cord, and mild loss of axons and myelin in the corticospinal tract. Trans-activation response DNA protein 43 (TDP-43) immunoreactive cytoplasmic inclusions, the pathognomonic findings for ALS, were noted in the nucleus facialis, nucleus ambiguus, and in the anterior horn of the spinal cord. In addition, Lewy bodies and Lewy neurites were found in the brainstem and in the nucleus intermediolateralis of the thoracic cord. The concomitant alpha-synuclein pathology may have been partly related to possible autonomic dysfunction underlying the two episodes of cardiac arrest.

Sjögren syndrome presenting with encephalopathy mimicking Creutzfeldt-Jakob disease.

A 61-year-old man developed subacute progressive dementia, general fatigue, a tonic-clonic seizure, and a decreased level of consciousness. He had a past history of chronic hepatitis type C and was diagnosed as having hepatic encephalopathy due to hyperammonemia. His level of consciousness did not improve even though the serum ammonia level improved. In addition, he had repeated general myoclonic seizures. Head MRI (diffusion-weighted imaging) showed high signal intensities in the right thalamus and the cerebral cortices in the frontal, temporal and parietal lobes (predominantly on the right side). An electroencephalogram (EEG) showed periodic lateralized epileptic discharges (PLEDs). Cerebrospinal fluid analysis revealed high total tau protein and 14-3-3 protein levels. This case was diagnosed as Creutzfeldt-Jakob disease (CJD) based on these clinical data. However, the patient gradually improved without specific treatment. The differential diagnosis was reconsidered, and an increased erythrocyte sedimentation rate and positive serum anti-SS-A and anti-SS-B antibodies were noted. A diagnosis of Sjögren syndrome (SjS) was finally made based on a biopsy of a minor salivary gland showing infiltration of lymphocytes around the gland ducts. Steroid therapy (prednisolone 40mg/day orally) was given, and his clinical condition improved. The lesions on the head MRI decreased, and the EEG findings normalized. This case suggests that SjS has a wide spectrum, including neurological disorders, and that SjS should be considered in the differential diagnosis of CJD.

Top of the basilar syndrome in a young adult initially presenting with a convulsive seizure.

A 23-year-old man was admitted to our hospital due to loss of consciousness and a generalized convulsive seizure. He was diagnosed as having primary epilepsy and treated with antiepileptic drugs. Emergency CT scan of the head showed no abnormality. However, MRI scan of the head several days after admission revealed fresh infarctions caused by occlusion of the basilar artery, i.e., "top of the basilar" syndrome. This case indicates the need for precise differential diagnosis of convulsive seizure in an emergency situation. It should also be borne in mind that basilar occlusion with 'onset seizure' can occur even in young adults who have no risk factors for stroke.

Cerebral white matter damage in frontotemporal dementia assessed by diffusion tensor tractography.

INTRODUCTION: We used diffusion tensor imaging (DTI) to study white matter integrity in patients with frontotemporal dementia (FTD). METHODS: The subjects comprised 20 patients (9 men, 11 women) with FTD and 17 age-matched healthy controls (9 men, 8 women). Based on the data obtained from DTI, we performed tractography of the major cerebral pathways, including the pyramidal tracts, genu and splenium of the corpus callosum (CC), bilateral arcuate fasciculi (AF), inferior longitudinal fasciculi (ILF) and uncinate fasciculi (UF). We measured the values of fractional anisotropy (FA) in each fiber and statistically compared the findings in patients with those in controls. RESULTS: We found a significant decrease in FA values in the selected association fibers as well as anterior fibers of the CC in the patients with FTD. The greatest decrease in mean FA of the UF was seen in advanced FTD. On the other hand, there were no significant differences in FA in the bilateral pyramidal tracts. CONCLUSION: The features of FTD from the view point of cerebral white matter damage were revealed by tractography based on DTI. DTI is therefore considered to be a useful method, and may provide clues to elucidating the pathogenesis of FTD.

Venous congestive myelopathy: three autopsy cases showing a variety of clinicopathologic features.

We describe three patients with progressive myelopathy, in whom autopsy revealed spinal cord pathology compatible with that of venous congestive myelopathy (VCM) associated with dural arteriovenous fistula (AVF), formerly known as angiodysgenetic necrotizing myelopathy (Foix-Alajournine syndrome). In these three patients, common symptoms were gait disturbance and sensory disturbance of the extremities, and these symptoms slowly worsened. The clinical diagnoses varied and included spinal cord intramedullary tumor, cervical spondylosis and multiple sclerosis. At autopsy, all the patients showed enlarged, tortuous venous vessels on the dorsal surfaces of the spinal cord at the affected levels. In the affected spinal cord parenchyma, necrotic lesions manifested by various degrees of neuronal loss and gliosis, with increased numbers of hyalinized vessels, were evident. The presence or absence of associated spinal dural AVF could not be identified histopathologically. Even with the help of modern neurological examination methods, early and accurate clinical diagnosis of VCM is sometimes difficult. When encountering patients with progressive myelopathy, VCM, although recognized as rare, should be considered as an important differential diagnosis.

Neuro-Behçet disease mimicking brain tumor.

Neuro-Behcet disease is one of the clinical forms of Behcet disease. We report a case of neuro-Behcet disease mimicked a brain tumor. This case was initially considered as a brain tumor from mass lesion with edema at left basal ganglia on radiologic images. The lesion, however, was not neoplasia by pathologic diagnosis. By using steroid therapy, the size had been markedly shrunken on the follow-up images. The clinical symptoms were also improved.