Lymphocyte subclasses and function in patients with optic neuritis in childhood with special reference to multiple sclerosis

Ten patients with childhood optic neuritis (5 with a single attack of ON and 5 with later MS) were studied at various stages of the disease. Lymphocyte count and function were analysed in the peripheral blood of all patients, 3 repeatedly, and in one they were also analysed in the CSF. T-lymphocytes counts were normal in all but 2 MS cases who had high counts. In acute stages the T4/T8 ratio were high in 1/3 determinations, in recovery low in 2/2 determinations, and in stable stages normal in 6/8 determinations. Lymphocyte function, measured by PHA, ConA and PWM stimulation, was normal in all but one. One patient showed significantly higher T-cell percentages and a high number of stimulated lymphocytes in CSF but a lower count of suppressor cells than in the blood. We found no abnormalities specific to MS nor to childhood MS or to disease activity stage. Rather than peripheral blood, it would seem more worthwhile to study CSF to clarify the pathogenesis of ON and MS.     

Assessment of MRI criteria for abnormal brain MRI in acute monosymptomatic optic neuritis. Comparison to findings in healthy persons

To evaluate various MRI criteria we studied a representative group of 149 consecutive patients below 50 years with acute monosymptomatic optic neuritis (AMON), a frequent first manifestation of multiple sclerosis (MS). The presence, number, size, and localization of areas of increased signal (AIS) on T₂-weighted brain MRIs obtained at 1.5 T were described and compared with findings in 71 healthy persons aged 21–50 years without diabetes, cerebrovascular or neurologic diseases. MRI was performed within 2–145 days, median 16 days from onset of AMON and showed from 0 to 26 AIS, sized 2–30 mm, in 79 of 149 (53%) patients compared to 0–18 AIS, sized 2–12 mm, in 31 of 71 (44%) healthy persons. In patients, AIS were significantly more frequent in women than in men (χ² = 4.67, p > 0.05). Periventricular AIS were revealed in 70 (47%) patients and in 14 (20%) healthy persons. Subcortical AIS were present in 5 (3%) patients and in 18 (25%) healthy persons. Infratentorial AIS were present in only 3 (2%) patients. The sensitivity and specificity of previously proposed diagnostic MRI criteria for MS were unsatisfactory in our group of patients and have previously only been validated in definite MS. We therefore constructed and tested four new sets of criteria. The set with the best relation between sensitivity (e.g. 41%) and specificity (e.g. 93%) was the following: presence of two or more AIS, of which at least one is periventricular or infratentorial, combined with the absence of subcortical AIS. These criteria are recommended for patients with AMON and might be used in other patients with possible or probable MS.     

Magnetization transfer imaging of multiple sclerosis

While conventional magnetic resonance imaging (MRI) measures signal primarily from the hydrogen nuclei of water, magnetization transfer (MT) MRI indirectly detects macromolecular associated hydrogen nuclei via their magnetic interaction with the observable water. In the normal adult CNS, white matter exhibits the largest MT effect due to the macromolecular content of the highly structured and lipid rich myelin. Pathologies which alter the structural integrity and the relative macromolecular-water composition, such as multiple sclerosis (MS), therefore show abnormal MT. Conventional MRI, which has a high MS lesion detection sensitivity but poor specificity in terms of differentiating the pathological state of a plaque, can thus be supplemented by MT to provide more specific information on the extent of demyelination and axonal loss. In this paper we review the basic concepts of MT imaging and its role in MS lesion characterization.Financial support was provided by the Medical Research Council of Canada, Fonds de la Recherche en Santé du Québec, and the Killam Foundation.     

A new technique for the treatment of lumbar far lateral disc herniation: technical note and preliminary results

A newly designed technique for a minimally invasive approach to the laterally herniated disc is presented. Fifteen patients suffering from far lateral disc herniation (extraforaminal) were operated according to this technique. Through a small skin incision (1.5 cm), the paraspinal muscles are spread by dilators, until a working channel of 9 mm inner diameter and 11 mm outer diameter can be placed. The next steps are done through this channel using the surgical microscope. No bone resections are necessary and the facet joints are left untouched. However, partial resection of the intertransverse ligament may be necessary. The mean follow-up period for these 15 patients was 11.5 months, and they were evaluated by using the visual analogue scale (VAS) and the Oswestry Disability Index (ODI). The average surgical time was 43 min. The ODI improved from 30.6 (preoperative) to 14.3 (postoperative). The VAS of leg pain improved from 7 (preoperative) to 3.6 (postoperative), which represented a statistically significant improvement at the significance level of (P<0.01). No intra-operative or early postoperative complications occurred. However, one recurrence did occur, which was treated by the same technique. This technique combines the advantages of three-dimensional visual control (operating microscope) with the minimal surgical trauma of endoscopic techniques, while avoiding some of the shortcomings of both the microsurgical and endoscopic techniques.     

Collagen abnormalities in the spinal cord from patients with amyotrophic lateral sclerosis

During the last 10 years, we have demonstrated morphological and biochemical abnormalities of skin extracellular matrices in amyotrophic lateral sclerosis (ALS). However, currently little is known concerning collagen of the spinal cord in ALS. We measured the amount of collagen and characterized collagen at light and electron microscopic levels in posterior funiculus, posterior half of lateral funiculus and anterior horn of cervical enlargement of the spinal cord obtained from ten patients with ALS, 11 patients with other neurologic diseases (control group A), and ten patients without neurologic ones (control group B). In posterior half of lateral funiculus and anterior horn, (1) by light microscopy, there was no significant difference in vessel wall area between ALS patients and control groups A and B; (2) ultrastructurally, collagen bundles were more fragmented and widely separated, and the fibrils were randomly oriented in the perivascular space of capillaries in ALS patients, which were not observed in any areas of control groups or in posterior funiculus of ALS patients; and (3) the collagen contents in ALS were significantly lower (P<0.001 and P<0.001, respectively) than those in control groups A and B. Fragmented and widely separated collagen bundles in the interstitial tissue surrounding capillaries and markedly decreased amount of collagen in posterior half of lateral funiculus and in anterior horn of ALS could be related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS, that is, selective neuronal vulnerability in ALS.     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

β-N-Acetylhexosaminadases in human cerebrospinal fluid and serum of patients with multiple sclerosis

β-N-Acetylhexosaminidase activity and isoenzyme have been investigated in normal human cerebrospinal fluid and that of patients with multiple sclerosis. β-N-acetylhexosaminidase activity in normal cerebrospinal fluids has been resolved into five components. The major component was in a form that eluted from DEAE cellulose at the same salt concentration as hexosaminidase As, the isoenzyme previously identified in human serum. Cerebrospinal fluid from patients exhibited a different isoenzyme profile, showing a remarkable increase in a form having a pI which was more acidic than that of As. These changes have a potential use in the diagnosis and further biochemical characterization of multiple sclerosis.     

No correlation between number of MRI-evident lesions in cerebrum and the soleus stretch reflex in multiple sclerosis patients

The aim of the study was to investigate if the stretch reflex of the soleus muscle was useful in quantifying upper motor neuron lesions. The soleus stretch reflex was recorded in 10 healthy subjects and 20 patients with active relapsing-remitting multiple sclerosis and correlated to the number of MRI lesions in cerebrum and clinical scores (expanded disability status scale and regional functional scoring system). The short latency stretch reflex was elicited by rotating the left ankle joint 4 degrees with a rise time in the interval of 40-640 ms. The amplitude of the stretch was larger in multiple sclerosis patients being 88.5 microV in patients and 12.8 microV in controls, P = 0.007. The sensitivity of the stretch reflex expressed as the slope of the best linear fit was increased in MS patients to 2.6 microVs/degree compared with 0.6 microVs/degree (0.1-2.2) in controls, P = 0.009. There was no correlation between amplitude of the stretch reflex and number of MRI lesions (r = -0.03). In conclusion, the soleus stretch reflex might be useful to quantify spasticity but is not useful in detecting dysfunction of upper motor neurons in MS.     

脊柱后入路显微内窥镜下手术治疗侧隐窝狭窄

目的 探讨脊柱后入路显微内窥镜下手术治疗侧隐窝狭窄的手术方法。方法 采用自行研制的异型骨凿，于显微内窥镜下手术治疗38例确诊为侧隐窝狭窄的患。结果 经6～12个月随访，所有患均无神经损伤等并发症；疗效评价：32例，良5例，可1例。结论 本术式具有创伤小，对术后脊柱的稳定性破坏小，疗效确切等优点。