Varicella-Zoster Meningitis and Myelitis After Herpes Zoster Dermatitis Treatment With Amenamevir: A Case Series and Literature Review.

Varicella-zoster virus (VZV), known for causing chickenpox, establishes latent infections in neural tissues. Reactivation of VZV can lead to herpes zoster (HZ) and various neurological complications. In this report, we present four cases of VZV meningitis and myelitis following amenamevir treatment for HZ dermatitis with positive VZV DNA in cerebrospinal fluid (CSF) revealed by polymerase chain reaction (PCR). Three of them were considered immunocompromised hosts given the fact that two of these patients were taking immunosuppressive drugs for rheumatoid arthritis, and one patient had a history of sigmoid colon cancer (four months after resection). After HZ onset, amenamevir, which has poor CSF transfer, was prescribed for all the patients, and all of them developed central nervous complications by VZV (meningitis in three cases and myelitis in one case) confirmed by PCR. All the patients were treated with acyclovir, which has a higher CSF transfer, and fully recovered. We speculate that amenamevir might have failed to prevent VZV infection in the central nervous system (CNS) and think that consideration should be given to administering acyclovir in preference to amenamevir for ΗΖ patients at high risk of CNS VZV infection, such as immunocompromised hosts.

A case of acute autonomic and sensory neuropathy (AASN) with antibody against a mixture of galactocerebroside and phospholipids.

A 62-year-old woman presented with paresthesia of limbs, gait disturbance, urinary retention and constipation following upper respiratory infection. Neurological examination revealed gait disturbance due to loss of position sense in her extremities with intact muscle power, and autonomic failure represented by orthostatic hypotension, constipation and autonomic bladder. Cerebrospinal fluid analysis showed normal cell counts with elevated protein levels. Nerve conduction study showed sensory nerve impairment with almost normal motor nerve conduction in her upper and lower extremities. Sympathetic skin response of both hands was unresponsive, indicating autonomic nervous dysfunction. We diagnosed her as having acute autonomic and sensory neuropathy (AASN) and treated her with intravenous immunoglobulin, which ameliorated her symptoms enabling her to walk without any assistance at the time of discharge. Screening tests of serum autoantibodies revealed positivity of antibody against a mixture of galactocerebroside (Gal-Cer) and phospholipids. According to previous literature, no specific antibodies have been identified in AASN. This case, therefore, suggests a possible role of anti-Gal-Cer antibody in the pathogenesis of AASN.

An adult-onset multiphasic disseminated encephalomyelitis (MDEM) presenting favorable response to steroid therapy.

A 64-year-old man presented with acute onset of generalized seizure and encephalopathy. FLAIR images of brain MRI showed multifocal high-intensity lesions of the white matter. Within few days after the treatment with intravenous methylprednisolone (1,000 mg/day for 3 days), amelioration of clinical symptoms and recovery of MRI findings were observed. Six months after the withdrawal of oral steroid therapy, recurrent lesions were observed at the same locations as initially revealed on admission. Due to the concomitant development of peripheral lymphocytosis, a brain biopsy was performed from a right frontal lesion. Histological findings suggested extensive demyelination accompanied by infiltration of inflammatory lymphocytes and macrophages. In spite of the temporary remission after re-initiation of oral steroid therapy, reduction of oral steroid dosage resulted in new lesion formation apart from the initial locations. Based upon clinical features, MRI findings and histological examination, he was diagnosed with multiphasic disseminated encephalomyelitis (MDEM). Acute disseminated encephalomyelitis (ADEM) is one of common causes of demyelinating disease among children. However, multiphasic form of ADEM is particularly rare in adult patients. Here we reported a rare case of adult-onset MDEM, in which clinical, radiological and histological features were described, and efficacy of steroid therapy was highlighted.

A case of relapsing encephalitis positive for gamma aminobutyric acid (GABA)A receptor antibody associated with Type B3 thymoma.

A 87-year-old female presented with subacute progression of cognitive decline. Fluid-attenuated inversion recovery images of brain MRI showed multifocal high-intensity lesions. Thoracic CT image revealed the presence of thymoma, and serum autoantibody screening showed positivity for anti-gamma aminobutyric acid (GABA)A receptor antibody. Histopathological analysis confirmed type B3 thymoma after thymectomy. The patient received both plasmapheresis and intravenous methylprednisolone therapy, and showed remarkable amelioration of clinical symptoms and MRI abnormal high intensity. However, after 2 month from the clinical recovery, the patient showed recurrence of brain lesions and intravenous methylprednisolone monotherapy was performed. Continuation of oral steroid therapy was required to maintain the quienscent state of inflammation within the central nervous system. Anti-GABAA receptor antibody is a recently discovered novel autoantibody associated with autoimmue encephalitis. Due to the limited number of literature reported, clinical course and therapeutic response of GABAA receptor antibody encephalitis remains elusive. Here we reported a rare case of GABAA receptor antibody encephalitis with type B3 thymoma. Clinical, radiological and therapeutic courses described in our report highlight the importance of immunotherapy for treatment of the disease.

The Motor Unit Number Index of Subclinical Abnormality in Amyotrophic Lateral Sclerosis.

PURPOSE: Diagnosis of amyotrophic lateral sclerosis (ALS) at an early stage is challenging, thus making the enrollment of these patients in clinical trials infeasible. In this study, we investigated the potential usability of motor unit number index (MUNIX) to detect denervation of clinically intact muscles of ALS patients. METHODS: Thirty-two first dorsal interosseous muscles of 26 ALS patients were evaluated with both MUNIX and needle electromyography. RESULTS: The mean MUNIX value of first dorsal interosseous muscles was 131 in the control group, whereas it was 48, 34, 15, and 8 for Medical Research Council scales of 5, 4, 3, and 2, respectively, in the ALS patients. The optimal cutoff point gave a sensitivity of 0.89 and a specificity of 1.0. Among 9 intact first dorsal interosseous muscles of the ALS patients, 8 showed MUNIX values below the cutoff point, whereas only 2 first dorsal interosseous muscles showed denervation on needle electromyography. CONCLUSIONS: MUNIX could serve as a sensitive technique to detect denervation of clinically intact muscles of ALS patients.

[Reversible hepatic myelopathy: a case report].

We report a case of reversible hepatic myelopathy. A 42-year-old female patient with 3-year history of alcoholic liver cirrhosis developed spastic gait, hyperreflexia and mild somatosensory disturbance in her lower extremities. The increased level of serum ammonia and the deficits of N30 and P38 in the tibial somatosensory evoked potentials (SEP) in conjunction with exclusion of the other known causes of myelopathy supported the diagnosis of her hepatic myelopathy. The ammonia lowering therapy by the oral administration of lactulose successfully improved the spastic gait accompanied with the emergence of N30 and P38 in the tibial SEP. Although liver transplantation was known to be the only therapy for hepatic myelopathy in the literatures, our case showed that the ammonia lowering therapy can be effective for the early stage of hepatic myelopathy.

[Communication with ALS patients: neurosurgical approach].

By progression of the disease, motor neurons degenerate in patients with amyotrophic lateral sclerosis (ALS) eventually lose nearly all voluntary muscles in the body. They are awake and aware but cannot move or communicate (locked-in state). Since the function of the brain is preserved, one possible measure to support their communication is to interpret their motor intention by decoding (deciphering) brain signals and present it with external devices. This technology called "brain-machine interface (BMI)" is now close to clinical use in Japan and USA.In our system, we record electrocorticogram (ECoG) obtained with subudural electrodes during their motor imagery, decode it and determine the movement they intended. So far, one patient of ALS with severe paralysis, implanted with this electrodes, successfully operated the PC communication tool only by thinking.

[Risk factors for fractures in Parkinson's disease: a questionnaire survey].

This study investigated the risk factors for fractures in patients with Parkinson's disease (PD). A questionnaire specifically designed to examine these risk factors was mailed to 172 PD patients registered in our self-developed PD database. We subsequently received replies from 158 patients, 22(14.8%)of whom had experienced fractures after PD onset. A multiple logistic regression model was used to evaluate the responses, and together with the clinical information stored in our PD database, it was revealed that psychiatric symptoms and falls within 1 year of our investigation were statistically correlated with the occurrence of fractures (adjusted odds ratio: 4.8 and 3.6, respectively). Thus, these results emphasize that psychiatric symptoms are an essential risk factor for fracture in PD patients.

[Survey on the attitude toward genetic testing of neurologists certified by the Japanese Society of Neurology].

To clarify the attitude toward genetic testing for neuromuscular diseases, a questionnaire was sent to 4,762 neurologists certified by the Japanese Society of Neurology. By December 21, 2011, 1,493 questionnaires (31.4%) were returned. Of these, 1,233 (82.6%) had experienced genetic testing, but only 396 (26.5%) had referred to the guideline for genetic testing of the Japanese Society of Neurology (2009). The numbers of respondents who were positive, or more positive than negative for genetic testing for myotonic dystrophy type 1 (DM1), Huntington's disease (HD), and familial amyloid polyneuropathy (FAP) were 753 (50.4%), 915 (61.3%), and 980 (65.6%), respectively. The predominant reason for a positive attitude toward genetic testing was to confirm or exclude the diagnosis. Conversely, the predominant reason for a negative attitude toward genetic testing differed between the diseases. For DM1, it was to confirm the diagnosis without genetic testing. For HD, it was that genetic testing would not result in effective prevention or therapy. In FAP, it was that post-testing psychosocial support for the patient and their family was difficult. Common to DM1, HD, and FAP, a significant number of respondents (approximately 60%) felt it difficult to explain the negative aspects that might occur after the disclosure of test results. Concerning predictive or prenatal genetic testing, most respondents referred at-risk individuals to specialized genetic counseling clinics. In general, neurologists are likely to conduct genetic testing properly in consideration not only of the characteristics of the diseases but also of the circumstances of each patient and his or her family. To support neurologists who are involved in genetic testing, the guidelines should be more easily accessible. Many respondents wanted information on the institutions that provide genetic counseling and testing; however, financial support to such institutions is indispensable for fulfilling this requirement.

L-threo-3,4-dihydroxyphenylserine (L-DOPS) co-administered with entacapone improves freezing of gait in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by a variety of motor symptoms including freezing of gait (FOG), in which walking is transiently halted as if the patient's feet were 'glued to the ground'. Treatment of FOG is still challenging. Although L-threo-3,4-dihydroxyphenylserine (L-DOPS), a precursor of noradrenaline, has been on the market in Japan because of its beneficial effect for FOG, clinical use of L-DOPS has been far from satisfying. However, the fact that there were some responders to L-DOPS encouraged us to hypothesize that the enhancement of L-DOPS concentration in the brain by the co-administration of L-DOPS and a catechol-O-methyl transferase (COMT) inhibitor, which is expected to interrupt L-DOPS metabolism in the peripheral circulation, would be beneficial for FOG. Based on our hypothesis, we conducted a preliminary study with a small number of participants with FOG. Of the 16 PD patients with FOG who completed this study, group 1 (n=6) received L-DOPS co-administered with entacapone, which is a COMT inhibitor used worldwide as an anti-parkinson drug, group 2 (n=5) received entacapone alone, and group 3 (n=5) received L-DOPS alone. Only the patients in group 1 showed a significant improvement in FOG. Moreover, the beneficial effect was observed only in patients with levodopa-resistant FOG. This result supports our hypothesis, at least in patients with levodopa-resistant FOG, and shows that the co-administration of L-DOPS and entacapone could be a new strategy for FOG treatment.

[Approach of gene medical treatment in neurological diseases with the neurologist's. "Approach of support to the patients with inherited and incurable neurological diseases"].

Advancements in medical genetics have increased access to genetic diagnosis in clinical neurology and accompanying genetic counseling. However, its use has not yet spread and the frequency of general biochemistry inspection in medical treatment and by patients remains low. Many problems remain for doctors, though sociocultural and other various causes exist. Thus, a network of care specialists for inherited and incurable neurological diseases has been established, consisting of multi-occupational categories in medical treatment, health, and welfare such as clinical inheritance specialists, psychiatrists, public health nurses, and medical social workers, to meet the rise in availability of such methods. Businesses in areas such as training, consultation, and field research have arisen. An educational campaign for neurologists who have taken a central role in treatment of inherited and incurable neurological diseases, and related information have been disseminated to those working in fields related to regional welfare of neurological medicine, and patients are now supported totally by team and regional counseling. These new developments in support systems for inherited and incurable neurological diseases, have steadily achieved the respective goals. We aim to promote its evolution to a more advanced network to promote the independence of individual patients in the future.