Paraneoplastic neurological syndromes (PNS) are thought to be caused by autoimmune processes triggered by the cancer and directed against antigens common to both the cancer and nervous system. There are several clinical phenotypes in combinations with the neurological syndromes, origin of cancer and the specific autoantibodies. In most patients, the neurological disorder develops before the cancer becomes clinically overt together with autoantibodies. As these antibodies are associated with a restricted range of cancers, the presence of the antibodies requires physicians in charge to search the underlying cancers. The early cancer treatment and active immunotherapy tended to ameliorate the neurological symptoms, especially in those harboring antibodies against cell surface antigens like NMDAR, VGKC, VGCC. The group of PNS having antibodies against intracellular antigens might be caused via cytotoxic T cell activation.
Frontal Assessment Battery (FAB) is short neuropsychological battery for the bed side screening of frontal lobe function. Several studies have indicated that frontal lobe dysfunction is the main neuropsychological feature in Amyotrophic lateral sclerosis (ALS). We examined frontal lobe function in patients with ALS and in age-matched normal subjects by using the FAB. We examined 24 patients with sporadic ALS aged 66.0±10.1 years, with a mean disease duration of 2.0±0.7 years, a Mini-Mental State Examination score of ≥24, a normal self-rating depression score, no dyspnea, and no or only slight disturbances in speech, cutting food, and handling utensils on the ALS Functional Rating Scale. Total FAB score, similarity score, and lexical fluency score were significantly lower in ALS patients. Total FAB score did not correlate with age, disease duration, ALS Functional Rating Scale, spirometry, or blood gas analyses. These results suggest frontal lobe dysfunction in ALS patients.
Background: Little is known about the diagnosis and management of restless legs syndrome (RLS) in Japanese neurology clinics. Objective: To validate the diagnostic criteria of the International RLS Study Group (IRLSSG) and the treatment algorithm of the Mayo Clinic in a Japanese neurology clinic setting and to clarify the features of Japanese patients with idiopathic RLS. Methods: Patients with RLS symptoms were examined by a neurologist and the assessment included neurological examination, tests for periodic limb movements (PLM) and dopaminergic response, and the clinical diagnosis was made according to IRLSSG diagnostic criteria. Patients diagnosed with idiopathic RLS were treated with dopaminergic agents and the efficacy was evaluated. Results: The study subjects were 151 Japanese patients who presented with RLS symptoms. Idiopathic RLS was diagnosed in 113 patients, secondary RLS in 16 and RLS mimics in 22. The cause of RLS mimics was either myelopathy, radiculopathy or neuropathy in 11 patients. The mean age of patients with idiopathic RLS was 50.1 (SD 20.0) years, 63% were woman, 97% had daily RLS, 31% had family history (40% of the early-onset subgroup), 86% reported unpleasant sensations in the lower legs, 43% had PLM in the daytime suggested immobilization test, 81% suffered from insomnia, 49% had limitations of work and activities, 71% reported impaired mood, 27% had consulted physicians about their symptoms, 4% had been diagnosed with RLS, 73% improved after dopaminergic treatments, and 33% experienced complete remission. Conclusions: The clinical features of Japanese patients with idiopathic RLS were identical to those reported in western countries, which suggests that IRLSSG diagnostic criteria and Mayo Clinic treatment algorism are valid in Japanese neurology clinics. Both patients and physicians were not fully aware of RLS in this country. Neurological examination was important in excluding RLS mimics and making a diagnosis of RLS.
We report a 47-year-old woman with relapsed delayed radiation myelopathy (DRM), occurring 5 years and 10 years after radiation therapy for nasopharyngeal carcinoma at 37 years old. Sensations of pain and temperature had been disturbed in the right leg since 42 years old. MRI showed Gadolinium-enhanced lesion as a ring-like-enhancement of the spinal cord at C1-2 on T1-weighted image (T1WI), with high signal area and swelling of the spinal cord at the upper C1 to C6 areas on T2-weighted image. We diagnosed her as having DRM after considering the differential diagnosis, e.g., multiple sclerosis, spinal tumor and other neurological diseases. Her sensory symptoms quickly improved following therapy with prednisolone and warfarin. Although she remained healthy for a few years, dysesthesia of the neck on the right side appeared 5 years later after the first clinical occurrence. At this time, MRI demonstrated Gadolinium-enhanced lesion as a ring-like enhancement of the spinal cord at C2 on T1WI, but the area also differed from that of previous lesion; a high signal area and swelling of the spinal cord was also seen on FLAIR image of the medulla and upper C1 to C6. For recurrence of DRM, we administered prednisolone and warfarin. Thereafter, the patient recovered and the spinal cord lesion on MRI decreased markedly. The clinical course demonstrated that administration of prednisolone and warfarin might be effective for relapsed DRM.
CMTX1, the second most common type of inherited hereditary motor and sensory neuropathy (HMSN), is associated with mutations of the gene for the gap junction protein connexin 32 (Cx32). In this condition, central conduction velocity is known to be delayed, presumably because mutated Cx32 is expressed in oligodendrocytes. A 45-year-old man presented with a 5-year history of progressive gait disturbance due to leg muscle weakness. The family history revealed that the mother had also progressive gait disturbance in her early 40s, and the younger sister could not walk faster than before at the age of 41. On neurological assessment, the patient exhibited pes cavus, distal muscle atrophy and weakness, and absence of the knee and ankle jerks. Touch sensation was impaired in the both feet. Motor and sensory nerve conduction velocities were reduced to 30-36m/s with mild temporal dispersion. Sural nerve biopsy revealed diffuse loss of large myelinated fibers with the remaining large and intermediate nerve fibers being frequently surrounded by a thin myelin sheath. Onion bulb formation was only occasional and mild in degree. His hearing acuity was normal on pure-tone audiometry, but BAEP test demonstrated prolonged central conduction time (-I wave 1.8 milliseconds, I-V wave 6.4 milliseconds). The BAEP findings prompted us to choose Cx32 gene to analyze first to find a novel mutation of two (A and T) base pairs deletion at codons 277 and 278 (Met93fs). Thus, the present case indicates that Cx32 gene mutation should be targeted first in case of HMSN with abnormal BAEP.
A 28-year-old man was admitted to our hospital because of severe headache and diplopia. Enhanced CT of the head revealed defects of contrast enhancement in the superior sagittal sinus and the right transverse sinus. Accordingly, he was diagnosed as suffering from cerebral venous thrombosis. The patient made a good recovery after receiving anticoagulant therapy. Investigations revealed a high plasma lipoprotein (a) [Lp (a)] level of 142mg/dl. We thought that his high Lp (a) level was associated with a thrombotic tendency. His mother also had an elevated plasma Lp (a) level of 45mg/dl. Cerebral venous thrombosis of unknown etiology is not rare. In such patients, we should investigate the plasma Lp (a) level.
A 75-year-old man with diabetic nephropathy treated with hemodialysis visited to a medical office because of slight fever, and received intravenous glucose infusion without any vitamins. Thereafter, he noticed gait disturbance and began to tell inconsistent stories. He was admitted to our hospital due to aggravation of these symptoms. On admission, he was disoriented and not able to sit by himself because of severe truncal ataxia without weakness. He had also gaze direction nystagmus. Based on clinical features, we considered him as having Wernicke's encephalopathy (WE) and treated him with 100mg thiamine per day. The thiamine supply diminished these symptoms soon. Plasma thiamine level prior to the administration was 7ng/ml, which confirmed the diagnosis. MRI did not disclose any abnormalities frequently seen in WE. WE is a life-threatening disease, and 'early detection, early cure' is important for recovering without sequelae. The thiamine deficiency is often seen in dialysis patients because of dietary restrictions as well as its loss during dialysis. This case gives us the caution; when hemodialysis patients present acute/subacute gait disturbance and/or abnormal mental state, we should consider WE. Furthermore, high-risk patients, such as elderly patients under hemodialysis may need some supplement including thiamine even at preclinical stage.
The present study was conducted with 20 ALS patients and their caregivers with the aim of examining whether caregiver burden and the caregiver's quality of life were correlated to the patient's degree of functional impairment. Patients were divided into a relatively mild functional impairment group (score of 14-18 on the ALS Functional Rating Scale (ALSFRS)) and a severe ALS group (score of 0-3 on ALSFRS). For those in the high-score ALSFRS group, caregiver burden increased as the patient's degree of functional impairment progressed, but there was no correlation in the low-score group. Furthermore, caregivers in the high-score ALSFRS group had significantly more mental health problems. These findings suggest the need for mental health care and reduction of caregiver burden due to progression of functional impairment for caregivers of ALS patients still at a relatively early stage of the disease.
A 48-year-old-man had intense pain in the neck and muscle weakness in the left upper limb after he presented low grade fever and appetite loss for a week. Several days later, he developed intense pain and severe muscle weakness in bilateral upper limbs. Laboratory examination showed elevated liver enzyme levels. His muscle weakness was severe in the right upper limb and was moderate in the left upper limb. Deep tendon reflexes were decreased in the bilateral upper limbs. CSF showed albuminocytologic dissiciation. A diagnosis of neuralgic amyotrophy was made. His liver dysfunction improved gradually. IgM and IgG anti-GT1a antibodies were positive. Future studies are required to elucidate whether anti-GT1a antibody is associated with the primary pathophysiology of neuralgic amyotrophy.