The Diversity of Neurological Complications Associated with Herpes Zoster: A Retrospective Case Series of 26 Patients.

Objective This study clarified a variety of neurological phenotypes associated with varicella-zoster virus (VZV) reactivation. Methods This retrospective single-center study included consecutive patients with herpes zoster accompanied by neurological disturbances from April 2016 to September 2022. A comparative analysis was performed to examine whether or not the neurological phenotype and severity were associated with the distribution of herpes zoster, clinical and laboratory findings, and treatments. Results Twenty-six patients with a median age of 74 years old were enrolled. None of the patients had been vaccinated against herpes zoster. Of the 26 patients, 14 (54%) developed monoparesis, 5 (19%) developed meningitis, 5 (19%) developed encephalitis, 1 (4%) developed paraplegia, and 1 (4%) developed bladder and rectal problems. Monoparesis of the upper limb is associated with herpes zoster involving the cervical and thoracic dermatomes, whereas meningitis and encephalitis often occur in patients with herpes zoster in the trigeminal and thoracic dermatomes. Neurological disability was generally severe [modified Rankin Scale (mRS) score ≥3] on admission [17 of 26 (65%) patients]. Good recovery after admission was associated with a lower mRS value before the onset of neurological disability, clinical meningitis, and elevated cell counts and protein levels in the cerebrospinal fluid. Good recoveries were observed in patients with herpes zoster in the trigeminal or thoracic dermatomes more frequently than in other dermatomes. Conclusion This study revealed that VZV-related neurological complications are heterogeneous, commonly leading to severe disability and poor outcomes, and that neurological phenotypes and outcomes are related to the distribution of herpes zoster.

[Chronic inflammatory demyelinating polyradiculoneuropathy with myelopathy due to massively enlarged nerve roots].

We report a 77-year-old man who presented with numbness and weakness of the feet bilaterally, that had progressed over 13 years. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on the basis of nerve conduction studies and a sural nerve biopsy; however, he was inadequately treated and his weakness had progressed. At 76 years of age, he developed spasticity in the legs as well as bladder and rectal incontinences. Gd-enhanced MRI revealed severe compression of the cervical cord by massively enlarged nerve roots. A cervical laminectomy was performed to decompress the cervical cord. A fascicular biopsy of the C5 dorsal root showed a prominent lymphocyte infiltration and edema. Repeated methylprednisolone pulse therapy and IVIg ameliorated the weakness. We concluded that the main cause of nerve root hypertrophy in this patient was active inflammation.

Steroid-responsive demyelinating peripheral neuropathy associated with chronic lymphoproliferative disorders of natural killer cells.

We herein report the findings of a 67-year-old woman with steroid-responsive multiple mononeuropathy associated with chronic natural killer (NK) cell lymphocytosis. The patient developed progressive, asymmetric weakness and numbness in all four extremities in the course of a three-month period. Nerve conduction studies revealed asymmetric demyelination in both the motor and sensory nerves, and a biopsy specimen of the sural nerve showed a conspicuous difference in the demyelination between the neighboring fascicles and the infiltration of NK cells in the endoneurium. We considered the multiple mononeuropathy in this patient to have been caused by NK cell infiltration in the endoneurium, and the observed asymmetry might have been due to differences in the NK cell intrusion among the fascicles. Corticosteroid administration resulted in a rapid neurological, electrophysiological and hematological improvement. The rapid clinical amelioration that was observed after corticosteroid therapy suggested that the neuropathy in this case had been mainly caused by the mechanical compression of the endoneurial NK cells or the inflammatory cytokines that had been released by them.

[Systemic vasculitic neuropathy diagnosed by means of (18)F-FDG PET CT].

We report a 43-year-old man experienced numbness in the distal portion of both legs, which progressed over following two months. Neurological examination showed hypesthesia and muscle weakness in the distal portion of both legs. No abnormal findings were seen on blood test and whole-body contrast enhanced computed tomography (CT). Histopathological findings of the sural nerve and the peroneus brevis muscle showed decreased myelinated nerve fibers with scattered myelin ovoids, vascular occlusion in the epineurium, and inflammatory cell around the arteriole in the muscle bundle. These findings suggested falling in the category as non-systemic vasculitic neuropathy (NSVN). (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) revealed the increase of FDG uptake in the rectum. Inflammatory cell infiltration was found around the arteriole with fibrinoid necrosis in the histopathological specimen of the rectal mucosal biopsy. This result represented the diagnosis as systemic vasculitis. The diagnosis of NSVN may depend on the sensitivity of diagnostic procedure, and (18)F-FDG PET CT might be a useful tool to detect small or medium-sized vasculitis.

[Leptomeningeal gliomatosis with high levels of adenosine deaminase in the cerebrospinal fluid].

A 61-year-old man developed disturbance of consciousness for 2 weeks. He showed neck stiffness and hyporeflexia. Analysis of his cerebrospinal fluid (CSF) revealed pleocytosis and markedly reduced glucose contents. Adenosine deaminase (ADA) levels in the CSF were elevated (28.8 IU/l). Brain magnetic resonance imagings showed enhancement of the leptomeninges. Tuberculous meningitis was considered, but antituberculous drug was not effective. Repeated cytological analysis of the CSF demonstrated atypical cells with enlarged unevenly distributed nuclei and immunoreactive with glial fibrillary acidic protein. We diagnosed him as leptomeningeal gliomatosis. CSF ADA may be elevated in this rare disorder, and here we emphasize that repeated cytological analysis with immunohistochemical staining was useful for diagnosis.

[Vaccine-associated paralytic poliomyelitis showing biphasic motor paresis].

We report a 38-year-old man with vaccine associated paralytic poliomyelitis (VAPP) which showed unusual biphasic worsening. The patient developed mild paresis of left upper and right lower extremities, five weeks after the oral poliovirus vaccination of patient's son and two weeks after the intramuscular injection of mumps/varicella vaccine in the left triceps muscle for himself. Needle electromyography (EMG) of his left arm and right leg was not remarkable, and the weakness recovered almost completely in three weeks. However, four weeks after the needle EMG, severe weakness and muscle atrophy of the four extremities, accentuated at the left arm and right leg, developed again. Cervical MRI showed gadolinium-enhanced, T(2) high-signal intensity area in the left C4-C6 anterior horn, most prominent at the height of C5 spine. Significant elevation of serum anti-poliomyelitis type 2 neutralizing antibody confirmed the diagnosis of VAPP. Immunomodulatory treatment, intravenous immunoglobulin (IVIg), did not improve weakness. We consider that the second clinical worsening of this patient was provoked by the needle EMG performed just after the first exacerbation, which injured the skeletal muscles and might have enhanced the retrograde transport of poliovirus via neural pathway.

[Good response to intravenous immunoglobulin therapy in sensory dominant distal variant of chronic inflammatory demyelinating polyneuropathy].

A 46-year-old man experienced numbness and muscle weakness in the distal portions of both hands, which progressed over following three months. Neurological examination showed mild muscle weakness only in distal arms, hypoflexia or areflexia, and hypesthesia in glove and stocking distribution. Motor conduction study revealed markedly prolonged distal latency and abnormal temporal dispersion. Sensory nerve potentials were reduced or could not be recorded. Histopathlogical findings of the sural nerve showed several nerve fibers with thinning myelin sheath and mild reduction of myelinated fibers. These results suggested the diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP). Two weeks after intravenous immunoglobulin therapy, neurological deficits rapidly improved and electrophysiological abnormalities were also ameliorated. Thereafter, there was no clinical deterioration for two years without further treatment. Our patient suggested that immunomodulating treatment is needed for stopping the initial progression of neurological deficits, but maintenance therapy is not always necessary for keeping the remitting state in distal variant of CIDP.

[A case of POEMS syndrome with enlarged pancreas due to IgG4-related autoimmune pancreatitis].

A 57-year-old man developed bilateral hands and feet numbness, followed by weakness with the legs and skin pigmentation. These symptoms became gradually worsened, and we made a diagnosis of POEMS syndrome because of progressive polyneuropathy, skin changes, IgG lambda type monoclonal proteinemia, and elevated level of serum vascular endothelial growth factor (VEGF). Diffusely enlarged pancreas was noticed in computed tomography. Serological, radiological, and histological findings revealed enlarged pancreas was due to IgG4-related autoimmune pathogenesis. After high dose chemotherapy with autologous peripheral stem cell transplantation, his clinical manifestations, IgG lambda type monoclonal proteinemia, and elevated level of serum VEGF were improved, whereas diffuse enlargement of the pancreas did not change. This is the first case report of POEMS syndrome accompanied with IgG4-related autoimmune pancreatitis. Co-existence of monoclonal and polyclonal plasma proliferative changes in the present patient may provide keys to clarify common mechanisms shared by these two rare disorders, POEMS syndrome and IgG4-related autoimmune disease.

[Novel nutritional management regimen for very long-chain acyl-CoA dehydrogenase deficiency].

We report a novel regimen of nutritional management in 22-year-old woman with myopathic form of very-long-chain acyl-CoA dehydrogenase deficiency. This regimen is based on avoidance of fasting by frequent intake of carbohydrates and substitution of medium chain triglyceride for long- and very long-chain fatty acids. Oral intake of medium amount of long-chain fatty acid (300 kcal daily) was allowed, to facilitate compliance and to escape pigmentary retinopathy. After this nutritional management and lifestyle guidance about prevention of fatigue and starvation, the patient was free from severe rhabdomyolysis for more than three years, which had forced her to hospital management nine times in seven years.

[Case of painful muscle spasm induced by thoracic vertebral fracture: successful treatment with lumbar sympathetic ganglia block].

We report a 70-year-old man, who developed painful involuntary muscle contraction of the left leg after the lumbar discectomy, which exacerbated after a vertebral fracture of Th12. This involuntary movement was accompanied with the abnormal position of left leg simulating triple flexion response, and was induced by active or passive movement of his left knee and foot joints. Several drugs including benzodiazepines and dantrolene were ineffective, although treatment with baclofen or carbamazepine was effective. These findings suggest that hyperexcitability of the anterior horn cells following the disturbance of spinal inhibitory interneurons was involved. Electophysiological studies suggested the disturbance of left lumber nerve roots. The spinal root blocks from L3 to S1 were performed, after which the painful involuntary muscle spasm was resolved. The lumbar sympathetic ganglia block was also effective; suggesting that abnormal afferent neuronal input to spinal cord was caused by the nerve root trauma which triggered the formation of secondary abnormal network in the spine. Lumbar sympathetic ganglia block should be recommended to a therapeutic option for the refractory painful muscle spasm of the leg.

[A 61-year-old female who suffered from herpes simplex encephalitis with expanded cerebral lesions on MRI and prolonged clinical course--the diagnostic usefulness of PCR using biopsied brain tissue specimens].

A 61-year-old female developed left hemiparesis after the onset of high fever and a consciousness disturbance. Fluid attenuated inversion recovery (FLAIR) MR imaging showed high signal intensity lesions in the right temporal lobe, cingulate gyrus, and parietal lobe. Encephalitis caused by a herpes simplex virus (HSV) infection was suspected and the administration of intravenous aciclovir was thus immediately initiated. Her consciousness disturbance rapidly became exacerbated; however, the brain lesions progressively expanded to the midbrain and left hemisphere. The addition of intravenous high-dose corticosteroids to the treatment regimen ameliorated the consciousness disturbance. Although no HSV DNA was detected by repeated PCR using cerebrospinal fluid (CSF) specimens, real time PCR using a biopsied brain tissue specimens detected HSV type 1 DNA. A pathological examination showed destruction of the grey matter and a perivascular aggregation of lymphocytes, thus suggesting a diagnosis of necrotizing viral encephalitis. Immunohistochemical analysis did not reveal the presence of the HSV antigen. Hence, in the present patient failure of PCR or a serological diagnosis using CSF specimens can be ascribed to the paucity of viral particles in the brain. We therefore concluded that real-time PCR using biopsied brain tissue specimens is a novel, sensitive method for detecting causative agents in patient with prolonged and undiagnosed encephalitis.

[A case of diffuse idiopathic skeletal hyperostosis presenting dysphagia and restrictive ventilatory impairment].

We report a 65-years-old man suffering from slowly progressive dyspnea of four years' clinical history followed by dysphagia. His range of motion was severely restricted in the four extremities and trunk, however, neither motor weakness nor sensory disturbance was noted. Radiographic examination showed diffuse osteophyte formation in front of whole vertebrae but no apparent change was observed in the sacroiliac joint. These radiographic features suggested the diagnosis of diffuse idiopathic skeletal hyperostosis (DISH) in this patient. We consider that the restrictive ventilatory impairment in the present patient was due to the decreased thoracic cage compliance caused by hyperostosis of thoracic costovertebral joints, and the prominent osteophyte formation in front of the cervical vertebrae compressing esophagus was responsible for dysphagia.

[Delayed encephalopathy following acute fentanyl intoxicication].

We report an 84-year-old woman who suffered from acute fentanyl intoxication followed by delayed encephalopathy. She used fentanyl patch at her ached knee joint and stayed in the covered table with a heat source underneath. Serum concentration of fentanyl suddenly elevated and she developed coma due to acute fentanyl intoxication. She gradually recovered, however, she showed consciousness disturbance again at 15th day and developed neurological symptoms including mutism, pyramidal tract signs, frontal lobe signs and parkinsonism. These symptoms also steadily improved without specific treatment, and became able to talk with colleagues and walk with assistance at 90th day. We considered that delayed encephalopathy due to periodic anoxia caused by fentanyl intoxication occurred in the present patient; however, the neurological sequelae were relatively mild as compared with reported cases of carbon monoxide intoxication. Neuroprotective effect of fentanyl may have contributed to the better prognosis in the present patient.

[A sixty-year-old man suffering from multiple system atrophy with pneumatosis intestinalis].

We herein report a 60-year-old man demonstrating multiple system atrophy of the cerebellar type (MSA-C) with a five-year of clinical history, who developed severe constipation followed by watery diarrhea. An abdominal CT scan showed free air in the abdominal cavity and extensive pericolic gas accumulation in the ascending and transverse colon. He was diagnosed to have pneumatosis intestinalis (PI). The air in the abdominal cavity as well as in the wall of the colon thereafter disappeared after nine days' of conservative therapy. The presense of chronic idiopathic intestinal pseudo-obstruction due to severe dysautonomia and a longstanding bed-ridden state may have been the cause of PI in this patient. This is the first case report of PI associated with MSA; however, the association of PI may have been overlooked in this disorder because of severe constipation and diarrhea, the two cardinal symptoms of PI, which happen to also be two of the typical symptoms of MSA itself.

A patient of migraine-like headache with amnesia, pleocytosis and transient hypoperfusion of cerebral blood flow.

Pseudomigraine with pleocytosis (PMP) is an uncommon disease in Japan. The diagnostic criteria include at least one episode of transient neurological deficit accompanied or followed by migraine-like severe headache, cerebrospinal fluid (CSF) lymphocytosis, and normal neuroimaging. Both the etiology and the pathophysiology of PMP is not yet well defined. We report a 40-year-old man with a PMP-like syndrome. He came to our clinic because of severe throbbing headache and amnesia, and the examination showed CSF lymphocytosis of 23/mm3, a transient decrease of cerebral blood flow in the left thalamus. All the symptoms were completely resolved within 2 months.

A case of postprandial cluster-like headache with prolactinoma: dramatic response to cabergoline.

A 17-year-old boy without a significant past medical history presented with recurrent cluster-like headaches induced by meals for 3 years. Magnetic resonance images showed a pituitary tumor. Just after starting treatment with cabergoline, the headaches resolved completely and the patient has been absolutely free from such headache attacks for 2 years.

Cortical Activation during Reading Letter String in Normal and Reverse Directions: An fMRI Study.

In order to investigate the difference of cortical activation between reading letter string in normal direction and reverse direction, an fMRI study was conducted. In this study, the cortical activations responsible for Japanese string and Chinese string reading were investigated. The subjects performed normal direction reading task (read strings from left to right), and reverse direction reading task (read strings from right to left). According to the experimental results, the activated brain regions during normal direction reading task and reverse direction reading task were almost the same, besides, we found visuospatial transformation was involved in the reverse direction reading task, while this function was not significant during normal direction reading task.