Since classical studies by Babinski and Holmes, various symptoms have been described as cerebellar ataxia. Then, what are elemental factors underlying such symptoms? Here three pathophysiological characteristics are stressed. First, spatial incoordination in muscle activations occurs commonly in various limb movements and gaits, resulting in jerky and irregular movements. Second, deficits in anticipation lead to loss of accuracy and smoothness in limb movements, for most of movements are carried out at a high speed without visual feedback, and anticipatory and preprogrammed control by the cerebellum is necessary. Third, adaptation in reflexes is disordered. The gain of stretch reflexes during standing are exaggerated in patients with cerebellar ataxia compared with controls, causing large sways during walking. Among these elemental characteristics, dysfunction in anticipation and adaptation can be well explained by internal model theory, a hypothesis based on synaptic plasticity in the cerebellar circuits.
Non-invasive positive pressure ventilation (NPPV) has recently been applied to the patients with multiple system atrophy (MSA) with various respiratory complications including vocal cord abduction impairment and respiratory disturbance by the central origin. Any consensus guidelines on setting up the inspiratory positive airway pressure (IPAP) and expiratory one (EPAP), however, have not been raised yet. To investigate this problem, we made the upper airway tract model with moderately and severely narrow glottis using a training/test lung and the artificial vocal cord which was developed for a humanoid talking robot in Waseda University. The artificial vocal cord was molded out of a high performance thermoplastic rubber in imitation of the human larynx. Previous studies using with a high-speed camera and a sound analyzer showed that the artificial vocal cord resembled human larynx closely both morphologically and functionally. The opening and closing movements of the artificial vocal cord were observed fiberscopically under various conditions of IPAP (4-20cmH2O) and EPAP (4-10cmH2O). The maximal glottic width during inspiration and expiration were measured by a pair of calipers on the videomonitored display. Both of the moderately and the severely narrow artificial vocal cords without non-paralytic factors showed typical paradoxical movement showing adduction in inspiration and abduction in expiration, which is characteristic to vocal cord abductor impairment seen in MSA. In the model with moderately severe narrow glottis, this paradoxical movement was released under any positive pressures of continuous (CPAP) and bilevel (Bilevel PAP) modes. In the model with severely narrow glottis, however, there existed a threshold in setting up the optimal EPAP to release the paradoxical movement. In conclusion, EPAP-leading procedure seems to be preferable to IPAP-leading procedure to dilate the narrow glottis as a pneumatic splint in the managements of the patients with MSA presenting with a paralytic type of vocal cord abductor impairment.
A right-handed 75-year-old man was admitted to our hospital complaining of sudden speech difficulty. Neurological examination showed slight left facial palsy of central origin. Although his spontaneous speech was fluent and contained no phonological or verbal paraphasia, it was like telegraphic speech, omitting or misusing postpositional particles. There was no history of changing handedness or family history of sinistrality or ambidexterity. Brain magnetic resonance imaging revealed fresh infarction of the middle-lower part of the right precentral gyrus. The WAIS-R VIQ, PIQ, and total IQ scores were 108, 100, and 117, respectively. In the explanation of a four-frame comic strip of the SLTA, there were misuses of postpositional particles in both speaking and writing. There was about 10% misuse on 249 questions for inserting postpositional particles in sentences. He had difficulty in changing from active- to passive-voice sentences and vice versa. In this patient, the lesion of the middle-lower part of the right precentral gyrus might be important for the expression of agrammatism in crossed aphasia.
The patient was a 69-year-old man who had a two-year history of slowly-progressive gait disturbance, paresthesia of the distal legs and bilateral hearing impairment. Nerve conduction study showed symmetric motor-dominant axonal polyneuropathy of the legs. Gadolinium-enhanced brain and spinal cord MRI revealed bilateral vestibular schwannomas, and multiple small schwannomas in the cauda equina, the surface of spinal cord and lumbar muscles. Genetic examination disclosed a point mutation in the exon 2 (T161C: L54P) of the neurofibromatosis 2 (NF2) gene, and the diagnosis of NF2 was made. It has been reported that axonal polyneuropathy is frequently observed in patients with NF2. Therefore, it is possible that axonal polyneuropathy of the present patient may be due to the abnormality of the NF2 gene, but not to the direct compression of the tumors, because the localization of his schwannomas in the cauda equina and the spinal cord could not explain his symmetric polyneuropathy. Although this patient showed no characteristic clinical manifestations such as cutaneous lesions, gadolinium-enhanced brain and spinal cord MRI was useful for the detection of asymptomatic schwannomas. NF2 should be considered as a differential diagnosis in patients with axonal polyneuropathy, even if it is late-onset.
A 40-year-old man was admitted to our hospital because of dysarthria, difficulty swallowing, double vision and weakness of both upper extremities. There were no detectable anti-AChR antibodies. He was diagnosed with seronegative myasthenia gravis (SNMG) based on a positive edrophonium test and positive waning on repetitive stimulation. Thereafter serological examination detected anti-muscle-specific kinase (MuSK) antibodies and he was diagnosed with anti-MuSK antibody-positive MG. Three years after the onset, the patient developed rapidly progressing respiratory failure and fever. He was diagnosed with aspiration pneumonia caused by swallowing difficulty. He was treated with mechanical ventilation, plasma exchange and antibiotics. Laboratory tests on admission also demonstrated nephrotic syndrome. Renal biopsy specimens showed diffuse thickening of the basement membrane by PAS and PAM stain, and granular immunofluorescent deposits of IgG4 along the glomerular capillary walls. Therefore, he was also diagnosed with membranous nephropathy in addition to anti-MuSK antibody-positive MG. MG is sometimes complicated with nephrotic syndrome, however there has been no report of anti-MuSK-antibody positive MG complicated with nephrotic syndrome. It has been reported that anti-MuSK-antibodies are IgG4 and that membranous nephropathy is suggested to be an IgG4 mediated disease. Our findings suggest that IgG4 may play an important role in the pathogenesis of our patient.
Interferon-gamma release assay (IGRA) using specific tuberculous antigens is a rapid, specific and sensitive method for the detection of tuberculous infection, and usually done in peripheral blood sample. We examined IGRA in cerebrospinal fluid (CSF) in a patient strongly suspected of having tuberculous meningitis. A 53-year old woman had a month history of headache and fever with meningeal sign. Routine systemic bacterial, tuberculous and viral analyses all resulted in negative study except for increase of adenosine deaminase in CSF. Neither of antibacterial or antiviral treatments were effective, but she was successfully treated with antituberculous agents. In IGRA, the interferon-gamma concentration in her CSF was high in the background level and increased further after the antigen stimulation, suggesting theoretically that tuberculous antigen-specific T cells were presented in her CSF. IGRA of CSF in combination with peripheral blood-IGRA could be a useful and rapid method for diagnosing active tuberculosis in the central nervous system.
A male, 60 years of age, presented with transient left facial pain located within all three divisions of the trigeminal nerve. Magnetic resonance imaging (MRI) revealed a swollen left trigeminal nerve with gadolinium enhancement. Following schwannoma diagnosis, the patient received Gamma Knife radiosurgery, which proved effective against symptoms of neuralgia and enhanced lesions. A relapse of unsteadiness was noted 11 months after initial treatment. Furthermore, while MRI presented a normal trigeminal nerve, multiple enhanced white matter mass lesions around the lateral ventricles were observed. Lastly, pathological examinations revealed diffuse large B cell lymphomas. The administration of high-dose methotrexate followed with whole brain radiation therapy appeared to have remarkable effects. No recurrences were observed in a 30 month duration following secondary treatment. Malignant lymphoma may present as trigeminal neuralgia. The conclusions from our case report and another literature review follow a difficult to near impossible task of establishing a correct diagnosis without biopsy in the initial stages of trigeminal nerve tumors. Therefore, a careful MRI follow-up is necessary even if the tumors show a favorable response towards primary steroid treatment or Gamma Knife radiosurgery.
Excessive daytime somnolence is one of the common complaints in patients with myotonic dystrophy. Here we report a 60-year-old female case of myotonic dystrophy type 1 with narcolepsy due to medical condition. The size of the CTG repeat in the 3' untranslated region of the DMPK gene was 1,800-2,400 repeats. Brain MRI was normal. Polysomnography revealed sleep apnea and chronic alveolar hypoventilation. Multiple sleep latency tests revealed normal sleep latencies and sleep onset REM was not observed. Orexin/hypocretin in the cerebrospinal fluid was markedly decreased to an undetectable level. Such sleep-related disorders may worsen the quality of life and possibly cause sudden death in patients with myotonic dystrophy. Narcolepsy associated with myotonic dystrophy should be evaluated appropriately.