White matter hyperintensity in neurologically asymptomatic subjects

Recent advances in magnetic resonance imaging (MRI) technology have had a great impact on the delectability of minute, asymptomatic lesions of the central nervous system. The clinical significance and treatment modes of these lesions, such as white matter hyperintensity (WMH) lesions detected by T2 MRI, remain controversial. To address these problems, we retrospectively evaluated WMH lesions in relation to clinical parameters for 240 neurologically asymptomatic persons who had visited a hospital for a medical check-up of the brain. Proton and T2–weighted MRI were obtained using a 0.5 T superconducting MR imager using the spin echo technique with a repetition time (TR) of 2800 msec. An echo delay times (TE) of 40 msec was used for the proton MRI, and a TE of 100 msec was used for the T2-weighted MRI. The images were visually analyzed according to a four-point grading system. The MRI findings were correlated with clinical parameters including age, gender, presenting symptoms, and hypertension. The overall frequency of WMH increased with age. Grades 2 and 3 of WMH were more frequent in aged persons, whereas the occurrence of grade 1 WMH remained relatively constant across age groups. Based on multiple regression analysis, age was the most significant variable influencing the frequency of WMH, followed by hypertension. These results imply that WMH lesions may simply be a phenomenon of aging, or may be an indicator of prepathologic state in an ischemic brain.     

Vitamin B complex and vitamin B12 levels after peripheral nerve injury

The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control (n = 8) and six study groups (1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury;n = 12 for each group). Crush-induced peripheral nerve injury was per-formed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B12 in the injured sciatic nerve were signiifcantly greater at 1 and 12 hours after experimental nerve injury, while they were signiifcantly lower at 7 days than in control group. Tissue level of vitamin B12 in the injured sciatic nerve was signiifcantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration.     

Association of obesity with cerebral microbleeds in neurologically asymptomatic elderly subjects

Obesity is associated with an increased risk of cardiovascular disease, but few studies have investigated the effects of obesity on subclinical cerebrovascular disease. Cerebral microbleeds (CMBs) are radiological markers of cerebral small vessel disease and reflect underlying vasculopathy. In this context, we assessed whether obesity was related to CMBs and to CMB subtypes categorized by location. Neurologically asymptomatic elderly subjects (n?=?1,251; age????65?years) who visited for routine health check-ups were included in this study. Cerebral microbleeds were evaluated through T2*-weighted gradient-recalled echo MRI. The subjects were categorized into two groups depending on CMB location: strictly lobar and deep or infratentorial microbleeds. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria. A total of 120 (9.6?%) subjects were found to have CMBs. As the severity of obesity increased, the prevalence of CMBs increased. Compared with the normal weight group and after controlling possible confounders, the risk of deep or infratentorial microbleeds was significantly increased in the overweight group [odds ratio (OR) 2.32, 95?% confidence interval (CI) 1.19?C4.53], and the obese group (OR 2.17, 95?% CI 1.14?C4.13). However, the ORs for the strictly lobar microbleeds were not increased in either the overweight or obese groups. Obesity was associated with deep or infratentorial microbleeds. This finding suggests that obesity affects cerebral small vessels through arteriosclerotic vasculopathy. Based on our findings, we postulate that obesity is associated with the presence of subclinical and bleeding-prone cerebrovascular disease in the elderly.     

Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson's disease.

We sought to determine the pattern of cognitive deficits in patients with Wilson's disease (WD) with different type and degree of neurological involvement, and to interpret the findings in relation to the underlying pathology. A total of 67 WD patients were examined with a neuropsychological test battery assessing different aspects of cognitive processing. The patients were subdivided into three groups: neurologically asymptomatic, neurological with pure basal ganglia lesions, and neurological with more extensive pathology. The results were compared with 50 matched healthy controls. Patients with a neurological form of WD showed a mild but definitive impairment in all cognitive functions. In contrast, the neurologically asymptomatic patients showed no deficits when compared with normal controls. Multifocal pathology was associated with more severe cognitive deficits than selective basal ganglia lesions but did not contribute significantly to memory impairment. A range of cognitive functions, including frontal-executive ability, aspects of memory and visuospatial processing, are affected in the neurologically symptomatic WD patients. In contrast, no subliminal deficits were observed in the asymptomatic patients. The lesions of the basal ganglia seem to be of central importance in explaining the symptomatology.     

Intrathecal humoral immunologic response in neurologically symptomatic and asymptomatic patients with human immunodeficiency virus infection

We analyzed the intrathecal humoral immunologic response in 42 human immunodeficiency virus (HIV)-infected patients. Eighteen patients had clinical neurologic abnormalities, while the remaining 24 patients were neurologically symptom-free. Nine of the neurologically symptomatic patients at early infection had slight neurologic dysfunction; in nine other subjects at late infection, the neurologic impairment was moderate or severe. When compared with symptom-free patients, neurologically symptomatic patients had increased intra-blood-brain barrier (BBB) HIV-specific IgG (p less than 0.001) and total IgG synthesis (p less than 0.01) with oligoclonal bands (OCBs) in the CSF and/or serum (11/18 versus 3/24). At early stages of the infection, neurologically symptomatic patients showed increased total intrathecal IgG synthesis (9/9) coincident with OCBs in the CSF and serum (7/9) and slight mononuclear pleocytosis (7/9), but less frequent HIV-specific IgG production within the CNS (6/9). In advanced infection, the number of neurologically symptomatic patients with intrathecal HIV-specific IgG synthesis (8/9) was higher, while the number of those with increased total intra-BBB IgG synthesis (5/9; p less than 0.01), OCBs (4/9), and increased CSF leukocyte count (1/9; p less than 0.001) was lower than at early infection. Our data suggest humoral intra-BBB immunoactivation at early stages of HIV infection followed by declining B cell response within the CNS at advanced infection.     

Cognitive and psychiatric effects of vitamin B12 replacement in dementia with low serum B12 levels: a nursing home study

BACKGROUND: The aim of this study is to determine whether B12 replacement would ameliorate cognitive and psychiatric symptoms in elderly subjects with dementia and low serum B12 levels. METHODS: A test group (n = 28) of nursing home residents with low serum B12 levels (<250 pg/mL) and a matched comparison group (n = 28) with normal serum B12 levels (>300 pg/mL) were evaluated by blinded raters while the test group received intramuscular (IM) B12 replacement therapy. All subjects were assessed at baseline, 8 weeks, and 16 weeks with the Dementia Rating Scale, Brief Psychiatric Rating Scale, and Geriatric Depression Scale. RESULTS: Although B12 replacement produced significant improvement in hematologic and metabolic parameters, it yielded no significant effect on cognitive or psychiatric variables. A few subjects evidenced notable individual treatment responses; however, these were not statistically more frequent than in the normal B12 group. CONCLUSIONS: These results suggest that B12 replacement is unlikely to benefit cognitive or psychiatric symptoms in the vast majority of elderly dementia patients with low serum B12 levels.     

Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency

INTRODUCTION: Nitrous oxide is frequently used for anesthesia. It may cause spinal cord toxicity. CASE REPORTS: We report two patients who presented gait disorders after nitrous oxide anesthesia. Physical examination revealed arms and legs pyramidal syndrome and abnormal proprioception, consistent with subacute combined degeneration of the spinal cord. Serum vitamin B12 level was extremely low. The patients improved with parenteral treatment with hydroxycobalamin. CONCLUSIONS: The inactivation of methionine synthase and L methylmalonylcoA mutase by nitrous oxide has been previously demonstrated. Anesthesia-related exposure to nitrous oxide may induce neurologic disorders even in patients with no preliminary vitamin B12 deficiency.     

Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia.

Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.     

The peripheral neuropathy of vitamin B12 deficiency

Nerve conduction studies and sural nerve biopsy were performed on three patients with vitamin B12 deficiency and symptoms of peripheral neuropathy. The pathological findings were those of axonal degeneration; there was no evidence of demyelination. The patients were reviewed at intervals of 5-15 years commencement of treatment; progression of the neuropathy had been arrested by treatment, but in all cases residual neurological abnormalities persisted. In one patient with autonomic neuropathy, the postural hypotension resolved rapidly and fully with treatment.     

Longitudinal study of EEG and evoked potentials in neurologically asymptomatic HIV infected subjects

Serial electroencephalograms (EEGs) and multimodality evoked potentials (EPs) were performed along with neurological and neuropsychological evaluation, cerebrospinal fluid assessment and magnetic resonance imaging at 6 month intervals in 73 neurologically asymptomatic HIV infected subjects. The results were compared with 50 age- and sex-matched controls. EEG was abnormal in 2 subjects (3%) initially and was abnormal in 7 (9%) subjects by the last examination. EEG abnormality (diffuse slowing) correlated significantly with slowed reaction time in neuropsychological testing (P<0.05). VEP and BAEP provided low yields of 1.3% and 4% respectively. SEP was abnormal in 7 (9%) of the subjects initially and in 10 (13%) subjects by the last testing, with 80% of the abnormalities seen on the posterior tibial study. In 3 subjects, initial SEP abnormalities predicted later development of myelopathy and peripheral neuropathy.Event-related auditory evoked potentials were performed in 39 subjects. They were abnormal in 5 subjects initially (12%) and in 6 subjects (15%) by the last examination and more commonly in advanced stages of the illness with lower T4 counts. This data shows the evolution and association of electrophysiological abnormalities in early HIV infection and suggests a predictive value for SEP in HIV infected asymptomatic individuals.     

Central sensory and motor conduction in vitamin B12 deficiency.

Four patients with subacute combined degeneration were studied through upper and lower limb SEPs recorded with a non-cephalic reference montage and through cortical and spinal magnetic stimulation. Clinical signs were confined to the lower limbs in 3 patients; the remaining patient presented only paraesthesiae in 4 limbs. Median nerve SEPs showed a normal cervical N13 response with a significant increase of central conduction time concerning exclusively the P9-P14 interpeak interval. Central motor conduction to upper and lower limb muscles was abnormal. Nerve conduction studies provided no evidence of peripheral nerve involvement. These electrophysiological findings suggest that in vitamin B12 deficiency the higher segments of the cervical cord are usually affected first and that central sensory and motor conduction studies are sensitive methods for detecting such damage.     

帕金森病患者周围神经病变与血清叶酸维生素B_(12)水平的相关性

目的分析帕金森病患者周围神经病变与血清叶酸、维生素B12水平的相关性。方法随机选取100例帕金森病患者为病例组,同时选取与病例组性别、年龄、身体条件、生活区域相似的100例健康人为对照组,比较2组周围神经病变的发病情况以及血清叶酸、维生素B12水平。结果病例组周围神经病变发病率42.0%,对照组为16.0%,病例组明显高于对照组(P0.05)。病例组尺神经、正中神经传导速度虽较对照组有所降低,但差异无统计学意义(P0.05);病例组周围神经受损者的腓肠神经、胫神经传导速度明显较对照组低(P0.05),但病例组无周围神经受损者的腓肠神经、胫神经传导速度较对照组虽有所降低,但只与对照组无周围神经受损者差异有统计学意义(P0.05)。对照组维生素B12以及叶酸的浓度较病例组高,且其浓度与病例组患者的周围神经受损程度有明显的正相关性;病例组无周围神经受损者的维生素B12以及叶酸浓度较对照组中周围神经受损者低(P0.05)。结论帕金森病患者周围神经病变与血清叶酸、维生素B12水平呈负相关,患者血清叶酸、维生素B12水平越低,发生周围神经病变的可能性越大,病情越重。     

血清叶酸、维生素B12水平与脑梗死的关系

目的为探讨血清叶酸、维生素B12水平与脑梗死的关系.方法运用放射免疫分析法检测50例脑梗死患者和44例正常对照组的血清叶酸、维生素B12浓度.结果脑梗死组血清叶酸、维生素B12浓度分别为(5.97±1.96)μg/ml、(511.47±212.06)μg/ml;对照组分别为(8.08±2.25)μg/ml、(806.91±254.60)μg/ml.脑梗死组血清叶酸、维生素B12水平均明显低于对照组,两组有显著性差异(P＜0.01).结论提示血清叶酸、维生素B12水平下降与脑梗死的发生有关,可能是其中又一危险因素.     

Homocysteine,vitamin B12 and folate levels in Iranian patients with ischemic stroke

Abstract

Objectives: Homocysteine, folate, and some group B vitamins have been proposed as a cause of Cerebro-Vascular Accidents (CVA). We conducted a case-control study to compare the plasma levels of folate, vitamin B12 and homocysteine in Iranian subjects with and without cerebro-vascular accident.

Methods: We recruited 82 patients with ischemic stroke as cases and 60 subjects as controls (using simple nonrandom sampling). Homocysteine was measured by fluorimetric high-performance liquid chromatography. Plasma folate and vitamin B12 levels were measured by an ion-capture method.

Results: Mean plasma level of vitamin B12 in cases and controls were 358.4±290.3 Pg/ml and 369.8±110.4 Pg/ml, respectively which did not show any significant difference. Mean plasma level of folate in cases was significantly lower than the controls (6.8±4.5 ng/ml vs. 12.2±3.0 ng/ml, p=0.001). It was also shown that mean plasma level of total homocysteine in cases was significantly higher than the controls (21.1±9.8 μM/L vs. 13.5±3.2 μM/L, P=0.001). Homocysteine and folate but not plasma B12 had linear relation with age. Male cases had significantly lower Folate and B12 in contrast to women. In addition, male cases had significantly higher Homocysteine level in contrast to women.

Conclusions: Our data shows that the level of homocysteine was higher and the level of folate was significantly lower in patients with ischemic stroke in contrast to controls. Effectiveness of supplementary folate and B 12 in such patients needs further well-structured prospective placebo controlled studies.     

Reversible peripheral neuropathy induced by vitamin B12 deficiency]

OBJECTIVE: To describe an electroclinical presentation of a peripheral neuropathy in a patient who suffered from vitamin B12 deficiency. PATIENT AND METHODS: We report the case of a 56-year-old man who, 17 years after a subtotal gastrectomy, presented with a diffuse sensory-motor demyelinating peripheral neuropathy with multifocal alteration of conduction confirmed by electromyography. Its causal relationship with vitamin B12 deficiency was biologically demonstrated. This neuropathy improved within a few days after intramuscular hydroxocobalamin treatment. Both clinical and electrophysiological signs had totally disappeared 3 months later on. CONCLUSION: This observation demonstrates that, in spite of its poor outcome reported by several authors, peripheral neuropathy induced by vitamin B12 deficiency can recover completely with substitutive treatment.     

Neuropsychology of vitamin B12 deficiency in elderly dementia patients and control subjects

Cobalamin deficiency may cause cognitive deficits and even dementia. In Alzheimer's disease, the most frequent cause of dementia in elderly persons, low serum levels of vitamin B12, may be misleading. The aim of this work was to characterize the cognitive pattern of B12 deficiency and to compare it with that of Alzheimer's disease. Nineteen patients with low levels of vitamin B12 were neuropsychologically evaluated before treatment and a year later. Results were compared with those of 10 healthy control subjects. Final results suggest that there is a different pattern in both diseases. Twelve elderly patients with dementia improved with treatment. Seven elderly demented patients did not improve; they deteriorated after 1 year although their levels of cobalamin were normal. Analysis of the initial evaluation showed that the 2 groups of patients had a different neuropsychological profile. The group that improved had initially more psychotic problems and more deficits in concentration, visuospatial performance, and executive functions. They did not show language problems and ideomotor apraxia, which were present in the second group. Their memory pattern was also different. These findings suggest that cobalamin deficiency may cause a reversible dementia in elderly patients. This dementia may be differentiated from that of Alzheimer's disease by a thorough neuropsychological evaluation.     

Orthostatic tolerance in older patients with vitamin B12 deficiency before and after vitamin B12 replacement

Abstract. Orthostatic hypotension (OH) and vitamin B12 deficiency are common disorders in older people. Several case series have reported an association between vitamin B12 deficiency and OH. The effect of vitamin B12 replacement on this dysfunction has not been studied. We prospectively studied responses to head up tilt in patients over 70 years with vitamin B12 deficiency (intervention group) and compared their responses after replacement to those of matched patients with idiopathic OH and normal serum vitamin B12 concentrations (control group). Blood pressure (BP), heart rate (HR) and systemic vascular resistance (SVR) changes during orthostatic stress were evaluated using digital artery photoplethysmography. Eight patients and eight controls were studied. Initial head up tilt produced a mean BP decrease of 44/29 mmHg (s. e. m. 4/4 mmHg) in the intervention group and 33/12 mmHg (s. e. m. 3/2 mmHg) in the control group. Repeat head up tilt 6 months after vitamin B12 replacement produced a mean BP decrease of 15/9 mmHg (s. e. m. 5/2 mmHg) in the intervention group. The mean decrease in the control group was 30/12 mmHg (s. e. m. 2/2 mmHg). The difference in BP decreases between groups was statistically significant for both systolic and diastolic BP (p < 0.001 for both systolic BP and diastolic BP). Mean SVR in the intervention group decreased by 658 dynes/cm⁵/ sec (s. e. m. 74 dynes/cm⁵/sec) during initial head up tilt. Mean SVR during repeat head up tilt decreased by 79 dynes/cm⁵/sec (s. e. m. 12 dynes/cm⁵/sec). Mean SVR in the control group decreased by 158 dynes/cm⁵/sec (s. e. m. 10 dynes/cm⁵/sec) during initial head up tilt and by 258 dynes/cm⁵/sec (s. e. m. 31 dynes/cm⁵/sec). The difference in SVR changes between groups was statistically significant (p = 0.02). We conclude that replacing vitamin B12 in older patients with vitamin B12 deficiency is associated with improved orthostatic tolerance to head up tilt.     

Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment--preliminary study

The vitamin B12 (VB12) parameter was studied in the serum and cerebrospinal fluid (CSF) of 14 demented patients. Eleven of these patients were in a state of dementia of the degenerative type such as Alzheimer's disease, senile dementia and Pick's disease. The serum VB12 concentration in all the patients was within normal limits, i.e. 500-1,300 pg/ml. There was no significant difference between the CSF-VB12 levels and the severity of dementia. The serum and CSF-VB12 levels of the demented patients did not show any significant elevation after the oral administration of CH3-B12, 2 mg per day. On the other hand, there was a marked elevation of both the serum and CSF-VB12 after an oral medication (2 mg per day) plus intramuscular administrations (500 micrograms per day). These results confirm that the intramuscular administration of CH3-B12 is an effective way to get a higher value of the serum and CSF-VB12 levels.