I here summarize the history of cerebellar stimulation experiments in humans and give some caution to use this stimulation method. In clinical evaluation, we consider the cerebellum as a kind of computer to get information from the peripheral structures and also higher motor cortical centers including the primary motor cortex (M1) and send a cerebellar command to M1 after computation of much information. We study functions of the cerebello-afferent and cerebello-efferent connections using cerebellar stimulation and differentiate these pathways dysfunction. We first activated the cerebellum using electrical stimulation. The most effective position, effective current direction and the interval of conditioning and test stimuli suggested that the observed effect might be produced by some cerebellar structures activation. Studies of cerebellar ataxia patients and other disorders supported the idea that the suppression is produced by the inhibition of dentato-thalamo-cortical pathway by Purkinje cell activation. In patients with a lesion at cerebellar hemisphere, dentate nucleus, superior cerebellar peduncle, motor thalamus, the suppression effect was not evoked. In contrast, the suppression was normally elicited in patients with a lesion at pontine nucleus, middle cerebellar peduncle even though they had clinically definite ataxia. Normal suppression was evoked in patients with non-cerebellar ataxia (sensory ataxia due to paraneoplastic syndrome, tabes dorsalis, ataxic sensory neuropathy). Based on these results, we concluded that the cerebellar electrical stimulation method was useful to differentiate cerebellar ataxia due to cerebellar efferent pathways lesions from other cerebellar ataxia and non-cerebellar ataxia. We demonstrated that magnetic stimulation over the cerebellum using a double-cone coil can produce the same effect as those elicited by electrical cerebellar stimulation. These all results supported the proposal that the magnetic stimulation over the cerebellum can enable us to differentiate the cerebellar efferent ataxia from other cerebellar ataxia and non-cerebellar ataxia. A recent paper has cautioned us to conclude the observed phenomenon to be produced by cerebellar activation after exclusion of several other factors as stated in the original paper2). The most serious factor to exclude is the antidromic activation of the corticospinal tracts by the cerebellar stimulation conditioning stimulus. To exclude this possibility, it is important how to measure the threshold of the corticospinal tracts. We recommend that we should use rectified EMG recordings when determining it. In summary, I conclude that the cerebellar magnetic stimulation is a good tool for physiological differentiation of cerebellar ataxia mechanisms in ataxic patients. At a current stage, I recommend a conservative method mentioned in the editorial paper22) for magnetic cerebellar stimulation.
We investigated the relationship between parosysmal atrial fibrillation (pAF) and left atrial (LA) size in patients with acute ischemic stroke. Between June 2006 and April 2008, we retrospectively enrolled 292 patients with acute ischemic stroke within 24 hours of onset, who measured LA size by transthoracic echocardiography. The patients were classified according to the presence or absence of chronic AF on admission (cAF and normal sinus rhythm (NSR) group). The NSR group was subdivided based on the pAF (pAF and non-AF group). We compared LA size among each groups. Furthermore in the NSR group, the factors associated with pAF were investigated by multivariate logistic regression analysis. Among the enrolled patients, cAF (cAF group) had 77 (26.4%), pAF (pAF group) had 32 (11.0%) and non-AF group was 183 (62.7%). The median of LA size of the cAF was highest (4.7cm), followed by the pAF group (4.1cm) and the non-AF group (3.5cm) (p<0.001). Median age (72.0 for the non-AF group vs. 74.5 years for the pAF group, p<0.001), NIHSS score on admission (3.0 vs. 12.5, p<0.001), D-dimer (0.6 vs. 2.1μg/ml, p=0.003), LA size (3.5 vs. 4.1cm, p<0.001) were higher in the pAF group than in the non-AF group. The optimal cut-off value, sensitivity and specificity of LA size to distinguish pAF from non-AF were 3.8cm, 68.6% and 73.8%, respectively. Multivariate logistic regression analysis demonstrated that a NIHSS score of ≥8 (odds ratio [OR], 4.399; 95% confidence interval [CI], 1.701 to 11.378, p=0.002), LA size of ≥3.8cm (OR, 8.882; 95% CI, 3.238 to 24.268, p<0.001) and mitral valvular disease (OR, 4.677; 95% CI, 1.720 to 12.720, p=0.003) were independent factors associated with pAF. We should consider the presence of pAF when LA size is over 3.8cm in acute ischemic stroke patients with sinus rhythm.
A 47-year-old man was admitted to the hospital because of general convulsion, loss of consciousness and hyperthermia. A diagnosis of acute heat stroke was made clinically and neuroradiologically. As the consciousness level ameliorated, he developed severe abulia and mutism, then cerebellar ataxic syndrome (viz. truncal ataxia, hypermetria, ataxic speech and nystagmus). An MRI (diffusion weighted image; DWI) disclosed abnormal diffuse high signal intensity of the cerebellar cortex with reduced apparent diffusion coefficient (ADC). Two months later after the onset, truncal ataxia and dysarthria significantly improved, while dysmetria of the extremities rather worsened. At that time, the abnormal signal intensity of the cerebellar cortex disappeared, and the cerebellum became atrophic. The cerebellar blood flow was significantly decreased on brain SPECT (99mTc-ECD). The abnormal DWI signal intensity of the cerebellar cortex in the present patient may represent the cytotoxic edema of Purkinje cells resulting from heat stroke-related hyperthermia. It is essential to repeat MRI examination for cerebellar pathology and to obtain better insight into sequelae in patients with acute heat stroke. Protirelin tartrate seemed to be valid for improvement of abulia in the present patient. Further study is indicated.
A 20 year-old woman with myotonic dystrophy type 1 (DM1) presented with fatigue, daytime somnolence, and sudden poor responsiveness. Blood glucose was measured before and after each meal for 4 days, and hypoglycemia was confirmed twice, although neither perspiration nor palpitations occurred in the hypoglycemic state. On a 75g oral glucose tolerance test (OGTT), fasting blood glucose level was 83mg/dl, and fasting blood immunoreactive insulin (IRI) level was 5.96μIU/ml. However, IRI increased to 528μIU/ml at 60 minutes and blood glucose decreased to 57mg/dl at 120 minutes of the OGTT. The patient was diagnosed with reactive hypoglycemia due to excessive insulin secretion. Oral administration of pioglitazone improved the excessive insulin secretion as assessed by OGTT. After starting treatment, hypoglycemia was not detected either pre- or post-prandially. After 10 months of treatment, blood glucose level after glucose loading was higher than fasting blood glucose level during OGTT, and the IRI area under the curve of the OGTT decreased. We considered that hypoglycemia unawareness resulted from recurrent hypoglycemic episodes in this patient. Pioglitazone was effective in improving hyperinsulinemia and reactive hypoglycemia in nondiabetic DM1.
A 44-year-old man presented with a 12-day history of severe non-throbbing headache. He showed no physical abnormality but obesity. On day 12, ring-shaped low intensity lesions inside straight sinus were revealed on T2*-weighted MRI image (T2*WI). On the following day (day13), he was found unresponsive at home, and ambulated with disturbed consciousness. FLAIR and diffusion-weighted MRI image disclosed high intensity signals in bilateral thalamus which were postulated as vasogenic edema. MR venography and conventional cerebral angiography showed an absence of flow in inferior sagittal sinus, vein of Galen, and straight sinus. These findings confirmed the diagnosis of cerebral venous thrombosis (CVT). Anticoagulant treatment was introduced and his consciousness level was gradually improved. On day 43, he was discharged with no neurological sequelae. A delay of correct diagnosis and treatment with CVT can lead to devastating disability or even to death. An early diagnosis of CVT is often dismissed owing to the nonspecific symptoms such as headache and nausea. Recent reports described high sensitivity of T2*WI for detecting CVT. Alterations in blood flow and oxyhemoglobin reduced products, deoxyhemoglobin, in thrombosed veins often produce the magnetic susceptibility on T2*WI. A detection of ring-shaped low intensity lesions within venous sinus on T2*WI were quite rare, and the signal changes of these sinus lesions were successfully visualized by chronological T2*WI. Taken together, our case implies that T2*WI is the powerful tool for the early detection of CVT, even before the critical symptoms might happen.
A 36-year-old man was hospitalized because of subacutely progressive gait disturbance. Neurological examination disclosed severe ataxia of gait and trunk and moderate ataxia of the four limbs, without signs of cognitive impairment. There were no manifestations of systemic infections. Brain MRI showed mild atrophy of the cerebellar vermis and hemispheres. Extensive laboratory search failed to disclose the cause of subacute ataxia. Cerebellar ataxia progressed, leading to the patient becoming wheelchair-bound two months after admission, when PCR analysis of the cerebrospinal fluid was positive for Epstein-Barr, JC, and hepatitis B viruses. In addition, the quantity of serum HIV1-RNA was 2.9×104copies, the absolute count of CD4+lymphocyte was 28/mm3, and the CD4/CD8 ratio was 0.04, despite clear denials by both the patient and his wife regarding any apparent infectious opportunities. Accordingly thereafter, highly active antiretroviral therapy was initiated. Several weeks after the initiation of therapy, ataxia stabilized with disappearance of serum HIV and cerebrospinal fluid JCV viral load. He returned to his occupation 20 months after disease onset without progression of ataxia or development of other neurological dysfunctions including dementia. We could not establish the exact pathogenesis of ataxia in this patient. It could have been primary cerebellar degeneration caused by HIV, or the other viruses detected (EBV, JCV) or autoimmune mechanisms caused by these viruses. However, HIV infection should be considered as an etiology in clinical setting of subacute ataxia, particularly in a young or immunocompromised patient.
We report a case of a 35-year-old man with histologically confirmed neurosarcoidosis who developed recurrent episodes of right-hemispheric dysfunction with diffuse cortical lesions of the right hemisphere on magnetic resonance imaging (MRI). A brain biopsy revealed granulomatous inflammatory cells in both the subarachnoid space and Virchow-Robin space, which might relate to the recurrent neurological dysfunction and MRI findings.
In order to clarify the clinical characteristics and effects of acetylcholinesterase inhibitors of patients with generalized myasthenia gravis with antibodies to muscle specific kinase (MuSK), we investigated seven patients with MuSK antibodies and eleven patients without both antibodies of acetylcholine receptor and MuSK. All patients with MuSK antibodies showed bulbar symptoms, which frequency was significantly higher compared to those in patients without double antibodies. The frequency of positive result of Tensilon test was significantly lower in patients with MuSK antibodies than in those without double antibodies. In response to intravenous edrophonium chloride, MuSK positive patients showed adverse reactions in a small dosage of edrophonium chloride, less than 5mg, such as fasciculation on facial muscles and stuffy sensation of throat. The adverse responses to a small dosage of intravenous edrophonium chloride injection is useful information to distinguish patients with seronegative generalized MG, whether they have MuSK antibodies or not. When acetylcholinesterase inhibitors medication is tried to patients with MuSK antibodies, if necessary, a small dosage of inhibitors should be used to avoid cholinergic hypersensitivity.
A 77-year-old woman was admitted with a chief complaint of tingling sensation in the both feet, which gradually developed just after the diagnosis of Castleman disease was made. Neurological examination showed mild weakness in the neck and pelvic girdle muscles, and sensory impairment affecting all modalities in the lower legs. Although these neurological findings suggest a diagnosis of neuropathy, nerve conduction studies (NCS) and F-wave disclosed no abnormalities. However, the short latency somatosensory evoked potential (S-SEP) in the tibial nerve revealed a significant delay in the P15 latency, which is indicative of neuropathy affecting proximal potion of the peripheral nerve. To our knowledge, only a few reports described proximal neuropathy associated with Castleman disease. In our case, the examination of S-SEP was very informative to make a diagnosis of neuropathy.