Clinical and MRI study of brain stem and cerebellar involvement in Japanese patients with multiple sclerosis

OBJECTIVES: To investigate the clinical and MRI features of brain stem and cerebellar lesions in Japanese patients with multiple sclerosis. METHODS: A retrospective study of 66 consecutive Japanese patients with multiple sclerosis (42 women and 24 men) was done by reviewing the medical records and MRI films. Forty nine patients were diagnosed as having clinically definite multiple sclerosis and 17 patients as having clinically probable multiple sclerosis according to Poser's criteria. Prevalence rates of each brain stem and cerebellar manifestation and frequency and distribution of MRI lesions in these patients were studied. RESULTS: Forty three patients (65%) had one or more infratentorial manifestations. Cranial nerves were clinically involved in 28 patients (42%), and most of the lesions were identified by MRI. Among them, manifestations of facial, trigeminal, and abducens nerves were relatively common. Cerebellar ataxia was found in 20 patients (30%). The MRI study showed that the lesions responsible for ataxia in these patients were mainly found in the cerebellar peduncles, but cerebellar hemispheric lesions were detected in only four patients (6.4%). CONCLUSION: The low frequency (6.4%) of the cerebellar MRI lesions in these patients is in sharp contrast with the figures reported for white patients with multiple sclerosis (50%-90%). Racial and genetic differences may have an influence on the susceptibility of each part of the CNS to demyelination in multiple sclerosis.     

Ocular microtremor in oculomotor palsy.

OBJECTIVES: Ocular microtremor (OMT) is a high frequency tremor of the eyes present in all individuals. Recent reports suggest that OMT may be a useful indicator of brainstem function. However, the actual origin of ocular microtremor remains controversial. This study aims to provide evidence that OMT has a neurogenic origin. MATERIALS AND METHODS: The OMT activity of five subjects with unilateral oculomotor nerve palsy and one subject with complete unilateral internal and external ophthalmoplegia were recorded from both eyes of each subject using the piezoelectric strain gauge technique, with the normal eye acting as a control. Five parameters of OMT activity were studied in each subject: the peak count, the power of the high frequency peak, the percentage power between 60 and 100 Hz, the percentage power between 70 and 80 Hz, and the 10 dB cut-off point. RESULTS: In the five subjects with oculomotor nerve palsy, the mean peak count in the normal eye was 88.4 Hz (SD+/-16.9) and in the affected eye was 59 Hz (SD+/-8.6), P < 0.0096. There was also a fall in the peak power, the power between 60 and 100 Hz, and the power between 70 and 80 Hz. In subject six, who had complete opthalmoplegia, there was no evidence of OMT activity in the denervated eye. CONCLUSIONS: These results suggest that innervation of the extraocular muscles is necessary for normal OMT activity, and OMT therefore has a neurogenic origin.     

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.     

Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis

The accepted standard treatment of relapsing multiple sclerosis consists of medications for disease symptoms, including treatment for acute exacerbations. However, currently there is no therapy that alters the progression of physical disability associated with this disease. The purpose of this study was to determine whether interferon beta-1a could slow the progressive, irreversible, neurological disability of relapsing multiple sclerosis. Three hundred one patients with relapsing multiple sclerosis were randomized into a double-blinded, placebo-controlled, multicenter phase I11 trial of interferon beta-la. Interferon beta-la, 6.0 million units (30 μg), was administered by intramuscular injection weekly. The primary outcome variable was time to sustained disability progression of at least 1.0 point on the Kurtzke Expanded Disability Status Scale (EDSS). Interferon beta-la treatment produced a significant delay in time to sustained EDSS progression (p equals; 0.02). The Kaplan-Meier estimate of the proportion of patients progressing by the end of 104 weeks was 34.9% in the placebo group and 21.9% in the interferon beta-la-treated group. Patients treated with interferon beta-la also had significantly fewer exacerbations (p = 0.03) and a significantly lower number and volume of gadolinium-enhanced brain lesions on magnetic resonance images (pvalues ranging between 0.02 and 0.05). Over 2 years, the annual exacerbation rate was 0.90 in placebo-treated patients versus 0.61 in interferon beta-la-treated patients. There were no major adverse events related to treatment. Interferon beta- la had a significant beneficial impact in relapsing multiple sclerosis patients by reducing the accumulation of permanent physical disability, exacerbation frequency, and disease activity measured by gadolinium-enhanced lesions on brain magnetic resonance images. This treatment may alter the hndamen- tal course of relapsing multiple sclerosis.     

Effects of oral glatiramer acetate on clinical and MRI-monitored disease activity in patients with relapsing multiple sclerosis: a multicentre, double-blind, randomised, placebo-controlled study

BACKGROUND: Parenterally administered glatiramer acetate reduces the frequency of relapses and the formation of active brain lesions seen with MRI in multiple sclerosis. This study assessed whether two doses of glatiramer acetate given orally could improve clinical and MRI measures of inflammation and neurodegeneration in a large cohort of patients with relapsing-remitting multiple sclerosis. METHODS: 1912 patients with relapsing-remitting multiple sclerosis were screened and 1651 were randomised to receive 50 mg or 5 mg of glatiramer acetate or placebo by daily oral administration over 14 months. The intention-to-treat cohort consisted of 1644 patients who took at least one dose of study medication (50 mg glatiramer acetate [n=543], 5 mg glatiramer acetate [n=553], placebo [n=548]). After baseline investigation, clinical assessments were done every 2 months and MRI was obtained for all patients at baseline and at study exit. Additionally, MRI was undertaken every 2 months for a cohort of 486 patients. The primary outcome was the total number of confirmed relapses observed during the study period. Several prespecified clinical and MRI secondary and tertiary outcomes assessed treatment efficacy on inflammation and neurodegeneration due to multiple sclerosis. FINDINGS: The cumulative number of confirmed relapses did not differ between the two active treatment groups and the placebo group. Relative to placebo, the rate ratio for the 50 mg glatiramer acetate treated group was 0.92 (95% CI 0.77-1.08, p=0.30) and for the 5 mg glatiramer acetate treated group was 0.98 (0.83-1.15, p=0.76). No drug effect was seen for any of the secondary and tertiary endpoints. The study drug was safe and well tolerated. INTERPRETATION: 5 mg and 50 mg glatiramer acetate administered orally on a daily basis do not affect relapse rate or other clinical and MRI parameters of disease activity and burden in patients with relapsing-remitting multiple sclerosis. Treatment with oral formulations of glatiramer acetate at the doses tested cannot be recommended.     

Stability and tremor in the fingers associated with cerebellar hemisphere and cerebellar tract lesions in man.

Stability and tremor in the fingers were assessed by a new technique in patients with unilateral cerebellar syndromes. In 11 patients with unilateral cerebellar hemisphere lesions tremor was observed with either clear tremor at 5-7 Hz or prolongation of the tremor profile out to 11 Hz. In 10 patients with unilateral cerebellar lesions associated with ipsilateral past-pointing there was an asymmetry in finger stability. Compared with normal subjects there was a significant decrease in stability contralateral to the lesion, while the ipsilateral side's stability was not different from normal. In patients with high brain stem lesions at the level of cranial nerves VII and above, tremor had frequencies of 5-7 Hz. In those with lower brain stem lesions, often with long tract signs as well, the frequencies of tremor were faster, 8-11 Hz, which may reflect damage to cerebellar inflow tracts. A broad if not specific correlation was found between clinical condition, site of lesion and finger stability and tremor.     

Inter- versus intra-subject variance in topographic mapping of the electroencephalogram

The variability of the normal topographic EEG distribution between a quiet, eyes closed, resting state and the performance of cognitive tasks (listening to a story or music) was studied in 20 normal (10 male) right-handed college students or graduates ages 18-40 yrs. Amplitude changes in the topographic frequency distribution (2.5-7 SD) of alpha frequency band (8-13 Hz) were noted between tasks and resting state in individual subjects. When group data for the resting versus listening states were compared, no statistical differences could be demonstrated. The group variability was 50% of the power of the resting record. Repeat studies in 10 subjects demonstrated a test-retest variance of 10% of the mean individual power. The data suggest that inter-subject differences in the alpha frequency and individual topographic differences will require careful normalization for development of baseline "brain maps" to serve as a standard for investigation of disease states.     

Clinical course of progressive multiple sclerosis in Brazilian patients

OBJECTIVE: To describe the clinical course and outcome of multiple sclerosis with progressive onset in Brazilian patients. A total of 238 medical records were reviewed, 26 cases (10.9%) fulfilled Thompson criteria (2000), and 5.80% classified as primary progressive and 5.04% relapsing progressive according to Lublin and Reingold. STUDY POPULATION: 19 Caucasians and 7 non-Caucasians; male:female ratio 1.2:1, mean age at onset was 34 +/- 7.9 years. RESULTS: Non-Caucasian patients had earlier onset of disease. The most common manifestations at onset were pyramidal and cerebellar (89% and 34.6%). After 11.3 +/- 6.35 years of disease more than 50% of the patients had involvement of most of their functional systems. No statistically significant differences were observed between the subgroups. CONCLUSION: The clinical course and outcome of progressive multiple sclerosis in Brazil, a tropical country with low prevalence, were very similar to those in the multiple sclerosis high prevalence areas.     

Bradykinesia akinesia inco-ordination test (BRAIN TEST): an objective computerised assessment of upper limb motor function

OBJECTIVES: A simple and rapid computerised keyboard test, based on the alternating finger tapping test, has been developed to quantify upper limb motor function. The test generates several variables: (1) kinesia score: the number of keystrokes in 60 seconds; (2) akinesia time: cumulative time that keys are depressed; (3) dysmetria score: a weighted index calculated using the number of incorrectly hit keys corrected for speed; (4) incoordination score: a measure of rhythmicity which corresponds to the variance of the time interval between keystrokes. METHODS: The BRAIN TEST(Copyright ) was assessed on 35 patients with idiopathic Parkinson's disease, 12 patients with cerebellar dysfunction, and 27 normal control subjects. RESULTS: The mean kinesia scores of patients with Parkinson's disease or cerebellar dysfunction were significantly slower than normal controls (Parkinson's disease=107 (SD 28) keys/min v cerebellar dysfunction=86+/- (SD 28) v normal controls=182 (SD 26), p<0.001) and correlated with the UPDRS (r =-0.69, p<0.001). The akinesia time is very insensitive and was only abnormal in patients with severe parkinsonism. The median dysmetria (cerebellar dysfunction=13.8 v Parkinson's disease=6.1 v normal controls=4.2, p=0.002) and inco-ordination scores (cerebellar dysfunction=5.12 v Parkinson's disease=0.84 v normal controls=0.15, p=0.002) were significantly higher in patients with cerebellar dysfunction, in whom the dysmetria score correlated with a cerebellar disease rating scale (r=0.64, p=0.02). CONCLUSION: The BRAIN TEST(Copyright ) provides a simple, rapid, and objective assessment of upper limb motor function. It assesses speed, accuracy, and rhythmicity of upper limb movements regardless of their physiological basis. The results of the test correlate well with clinical rating scales in Parkinson's disease and cerebellar dysfunction. The BRAIN test will be useful in clinical studies. It can be downloaded from the Internet ().     

Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates

We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.     

Guillain-Barré syndrome with cerebellar symptoms and elevated serum anti-GD1b IgG antibody]

We reported a 46-year-old woman with Guillain-Barré syndrome (GBS) after suffering from common cold. She also had cerebellar symptoms; ataxic speech, poor finger-nose and heel-knee tests, dysmetria, dysdiadochokinesis, poor one foot standing, positive Mann's test, ataxic gait, and poor tandem gait without Romberg's sign, and sensory disturbance. We ruled out other diseases with cerebellar symptoms; for example, Wernicke encephalopathy, multiple sclerosis, cerebellar vascular disease and encephalitis in the brain stem and cerebellum. Anti-GD1bIgG antibody was elevated in her serum in the acute phase. She was treated with immuno-adsorption therapy (TR-350) in the acute phase. The antibody titer decreased with clinical improvement after immuno-adsorption therapy. The involvement of the anti-GD1bIgG antibody in the pathogenetic mechanism of peripheral neuropathy and cerebellar symptoms was suggested.     

Quantitative multiple sclerosis plaque assessment with magnetic resonance imaging. Its correlation with clinical parameters, evoked potentials, and intra-blood-brain barrier IgG synthesis

Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS)     

A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis

OBJECTIVE: (a) To establish whether the cognitive decline of the early phase of relapsing-remitting multiple sclerosis depends on the progression of the burden of disease, or on the loss of brain parenchyma, or is influenced by both; (b) to monitor the loss of brain parenchyma in the early phase of the disease; and (c) to examine its possible relation with the progression of physical disability. METHODS: For 2 years 53 patients with clinically definite relapsing-remitting multiple sclerosis with disease duration 1-5 years and expanded disability status scale < or =5.0 at baseline were monitored. The neuropsychological performances, the psychological functioning, the neurological impairment, and the disability have been assessed at baseline and after 2 years. Patients also underwent PD/T2 and T1 weighted brain MRI. T2 and T1 lesion volumes were measured by a semiautomatic technique. Quantification of brain parenchymal volumes was obtained using a highly reproducible computerised interactive program. The relation between cognitive impairment and MRI findings has been investigated by partial correlation and stepwise multiple regression analyses excluding the effects of age, education, anxiety, depression, and total days of steroid use. RESULTS: In the 2 years of the study the mean change for T2 and T1 lesion volumes and brain parenchymal volumes were +1.7 ml (95% confidence interval (95% CI) 1.3-2.2, p=0.005, (29.8%); +0.2 ml, 95% CI 0.15-0.26, p=0.004, (25%); and -32.3 ml, 95% CI 24.2-42.3, p<0.0001, (2.7%), respectively. Overall, 14 patients (26.4%) were judged to be cognitively impaired at baseline and 28 (52.8%) at the end of the follow up. Of the 18 neuropsychological tests and subtests employed in the study, patients with multiple sclerosis failed 5.8 (SD 2.3) tests at the baseline and 8.4 (SD 2.9) (p<0.0001) tests at the end of the study. When the cognitive changes were examined in individual patients, five (9.4%) of them were considered cognitively improved, 33 (62.3%) remained stable, and 15 (28.3%) worsened over 2 years. T2 and T1 volume changes in improved, stable, and worsened patients did not show any significant difference, whereas brain parenchymal volume decrease in cognitively worsened patients was significantly greater (-66 ml (5.4%), 95% CI 37-108.9, p=0.0031). The cognitive impairment was independently predicted over 2 years only by the change of brain parenchymal volumes (R=0.51, p=0.0003). Ten patients (18.9%), who worsened by one or more points in the EDSS during the follow up period had significant decreases in brain parenchymal volumes (-99 ml (8%), 95% CI 47.6-182.3, p=0.005). At the end of the study the loss of brain parenchyma correlated significantly with change in EDSS (r= 0.59, p<0.0001). CONCLUSIONS: In the early phase of relapsing-remitting multiple sclerosis the cognitive deterioration relies more on the development of brain parenchymal volume atrophy than on the extent of burden of disease in the brain. The loss of brain parenchymal volume underlies the progressive accumulation of physical disability from the initial phase of the disease, which becomes more demonstrable only if studied with longer observation periods. Probably, the main pathological substrate of brain atrophy in the early stage of the disease is early axonal loss, which causes the progression of neurological deficits and the development of cognitive impairment. These data support the debated opinion that disease modifying therapy should be initiated as early as possible.     

Disturbed fluctuations of resting state EEG synchronization in Alzheimer's disease.

OBJECTIVE: We examined the hypothesis that cognitive dysfunction in Alzheimer's disease is associated with abnormal spontaneous fluctuations of EEG synchronization levels during an eyes-closed resting state. METHODS: EEGs were recorded during an eyes-closed resting state in Alzheimer patients (N=24; 9 males; mean age 76.3 years; SD 7.8; range 59-86) and non-demented subjects with subjective memory complaints (N=19; 9 males; mean age 76.1 years; SD 6.7; range: 67-89). The mean level of synchronization was determined in different frequency bands with the synchronization likelihood and fluctuations of the synchronization level were analysed with detrended fluctuation analysis (DFA). RESULTS: The mean level of EEG synchronization was lower in Alzheimer patients in the upper alpha (10-13Hz) and beta (13-30Hz) band. Spontaneous fluctuations of synchronization were diminished in Alzheimer patients in the lower alpha (8-10Hz) and beta bands. In patients as well as controls the synchronization fluctuations showed a scale-free pattern. CONCLUSIONS: Alzheimer's disease is characterized both by a lower mean level of functional connectivity as well as by diminished fluctuations in the level of synchronization. The dynamics of these fluctuations in patients and controls was scale-free which might point to self-organized criticality of neural networks in the brain. SIGNIFICANCE: Impaired functional connectivity can manifest itself not only in decreased levels of synchronization but also in disturbed fluctuations of synchronization levels.     

Acute transverse myelopathy in multiple sclerosis

Sixty-two consecutive patients with clinically definite multiple sclerosis (MS) were classified into 2 subgroups: group A, consisting of 16 patients who had shown acute transverse myelopathy (ATM) during the course of illness; and group B, 46 patients without ATM. The clinical features of these 2 groups were analysed prospectively for certain periods, and some significant differences were found. There was (1) later onset, (2) less frequent occurrence of brain stem, cerebellar and cerebral symptoms, (3) more frequent and severe involvement of the optic nerve, (4) a smaller proportion of patients with abnormal findings on brain MRI in group A compared with group B. The clinical features of group B were quite similar to those of previous Western series, while group A seemed to constitute a distinct clinical subgroup in patients with MS.     

Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease.

OBJECTIVE--To determine whether concentrations of soluble E-selectin (sE-selectin), an immunological marker of endothelial activation, were correlated with gadolinium-DPTA enhancement on MRI in patients with multiple sclerosis. METHODS--Serial sE-selectin concentrations were measured in 28 patients with multiple sclerosis undergoing monthly gadolinium (Gd) enhanced MRI of the brain and spinal cord, and in 10 control subjects. C reactive protein (CRP), von Willebrand factor (vWF), and tumour necrosis factor-alpha (TNF alpha) were also determined. RESULTS--Primary progressive patients had significantly increased sE-selectin concentrations compared with the relapsing remitting and secondary progressive patients who had normal sE-selectin concentrations (22.2 (SD1 6.1) ng/ml v 9.8 (SD2.1) ng/ml and 7.7 (SD2.7) ng/ml, respectively, P = 0.03). This difference was attributable to five of the 10 primary progressive patients who had persistently raised sE-selectin concentrations, with relatively inactive MRI studies. No correlation could be found between sE-selectin concentrations and Gd enhancement on MRI, but a close correlation existed between mean concentrations of sE-selectin and TNF alpha (r = 0.71, P < 0.001). Despite raised sE-selectin and TNF alpha concentrations, primary progressive patients had normal CRP concentrations (1.03 (SD1.14) mg/l), which were significantly lower than the relapsing remitting (3.16 (SD2.54) mg/l) and secondary progressive patients (2.28 (SD2.1) mg/l, P = 0.03). Raised CRP concentrations did correlate with infectious episodes, clinical relapse, and Gd enhancement, and were significantly raised when no MRI activity was found. Concentrations of vWF were normal in all patient groups. CONCLUSIONS--The results further high-light the differences between patients with primary progressive and those with relapsing remitting/secondary progressive multiple sclerosis.     

Brain stem auditory and visual evoked potentials in multiple sclerosis

The diagnostic value of the checkerboard pattern-reversal visual evoked potential (VEP) and the random, low rate stimulated brain stem auditory evoked potential (BAEP) was compared in 99 patients with established or suspected multiple sclerosis (MS). In normal subjects examined by both techniques no abnormal recordings were found. In 49 patients with definite MS an incidence of abnormality was found in 100% of VEP and in 84% of BAEP recordings. In 50 patients with probable or possible MS an abnormal VEP was found in 70% and an abnormal BAEP in 50%. When the two examinations were combined, the diagnostic yield increased to 100 and 80%, respectively. 22 patients had only spinal symptoms; in these the VEP gave 73%, the BAEP 55% and the combination 82% abnormalities. The combination of the two techniques was found useful for demonstrating demyelinating lesions in the central nervous system, the diagnostic value being greatest when these lesions were clinically silent.     

The muscle fiber conduction velocity and power spectra in familial hypokalemic periodic paralysis

Surface EMG has been used to determine the average muscle fiber conduction velocity (MFCV) and power spectra of the m. biceps of 10 patients and 15 asymptomatic offspring of a large kinship with familial hypokalemic periodic paralysis (HOPP). The MFCV of the patients was 3.37 +/- 0.35 m/sec (mean +/- SD, n = 9), the median frequency (Fmed) of the power spectra was 55.0 +/- 5.8 Hz (mean +/- SD, n = 9), both values are significantly (P0.001, Student's t-test) lower than the control values: MFCV = 4.55 +/- 0.33 m/sec; Fmed = 88.6 +/- 15.5 Hz (mean +/- SD). In 6 of the 15 asymptomatic relatives, the surface EMG results were also abnormal. It is concluded that the MFCV is reduced in familial HOPP. This results in a predominantly low-frequency content of the power spectra, thereby providing a new model for studying the relationship between the MFCV and the frequency spectrum of surface EMG. Asymptomatic relatives that have inherited the disease probably can be detected with this method.     

Keyhole aqueduct syndrome

Communicating syringes confined to the brain stem are extraordinarily rare. Two patients, presenting with signs and symptoms of cerebellar dysfunction, later developed evidence of brain-stem disease with dysarthria, nystagmus, deafness, and internuclear ophthalmoplegia. The condition of both patients had been diagnosed clinically as multiple sclerosis, but at autopsy they had a striking keyhole-shaped syrinx in the midbrain and upper pons, which communicated with the aqueduct and fourth ventricle without associated syringomyelia. In addition, both patients had marked atrophy and gliosis of the cerebellum, one with extension of the syrinx into cerebellar folia. The unique character of these lesions coupled with the similarity of the clinical features of the cases prompted us to name this disorder--"keyhole aqueduct syndrome."     

Non-invasive brainstem monitoring: the ocular microtremor

The ocular microtremor (OMT) is mediated by the oculomotor area of the brainstem and is altered in several pathologic states, including traumatic brain injury, general anesthesia, brain death, coma, Parkinsonism and multiple sclerosis. The EYETECT tremor monitor is a non-invasive means of measuring the frequency and amplitude of this microscopic tremor. It has been clinically tested in these clinical scenarios and has been found to be a reliable means of detecting the depth of anesthesia, and has been useful in predicting outcome in coma and traumatic brain injury patients and in confirming brain death. This paper reviews the scientific literature on the EYETECT OMT monitor, describes the underlying physiology and discusses the potential for future works and clinical use of this innovative technology.