Multiple sclerosis of the spinal cord: magnetic resonance appearance

OBJECTIVE: To determine the MR appearance of spinal cord multiple sclerosis (MS) plaques in patients presenting with myelopathy by using a high-field (1.5 T) imager. MATERIALS AND METHODS: We studied 119 patients who underwent high-field (1.5 T) MR studies of the spinal cord for evaluation of myelopathy. All 119 patients were thought to have possible findings of spinal cord MS at the time of the MRI interpretation. RESULTS: Sixty-four plaques were studied in 47 patients with clinically definite MS and adequate quality MRI. Of these patients 68% had a single spinal cord plaque, 19% had two plaques, and 13% had three or more plaques. Sixty-two percent of the plaques occurred in the cervical spinal cord and most frequently involved the posterior (41%) and lateral (25%) aspects of the spinal cord. None of the 64 lesions involved the entire thickness of the spinal cord. The lesion length varied from 2 to 60 mm, with 84% of the lesions < 15 mm in length. The spinal cord diameter was unchanged in 84% of plaques, enlarged at the level of the lesion in 14%, and atrophic in 2%. Just over half (55%) of the plaques enhanced with intravenously administered gadolinium. Of the patients who received synchronous head and spinal cord examinations on the same day, 24% had normal findings on the MR study of the head. Follow-up spinal cord studies were available in nine patients. New lesions developed in two patients, while previously described lesions resolved. In three patients only new lesions developed. In four patients no change occurred in the existing number of cord plaques. CONCLUSION: Spinal cord demyelinating plaques present as well-circumscribed foci of increased T2 signal that asymmetrically involve the spinal cord parenchyma. Knowledge of their usual appearance may prevent unnecessary biopsy. An MR examination of the head may confirm the imaging suggestion of spinal cord demyelinating disease, because up to 76% of patients have abnormal intracranial findings. In the remaining 24% of cases in which the clinical diagnosis is not certain and MR findings in the head are negative, a follow-up spinal cord study is recommended, because these lesions evolve and change over time.     

MR of spinal cord ganglioglioma

PURPOSE: Our purpose was to describe the MR imaging features in a series of spinal intramedullary gangliogliomas and to compare these findings with the MR features of intramedullary astrocytomas and ependymomas. METHODS: A retrospective analysis was performed of 76 MR examinations in 27 patients with histologically proved spinal ganglioglioma; these were then compared with imaging findings in a representative sample of histologically proved spinal cord astrocytomas and ependymomas. RESULTS: Statistically significant observations regarding spinal gangliogliomas included young age of the patients (mean, 12 years), long tumor length, presence of tumoral cyst, presence of bone erosion and scoliosis, absence of edema, presence of mixed signal intensity on T1-weighted images, and presence of patchy enhancement and cord surface enhancement. A trend (not statistically significant) was noted for holocord involvement and lack of magnetic susceptibility. CONCLUSION: Spinal ganglioglioma can be strongly suspected if MR images reflect the above criteria; however, the ultimate diagnosis still depends on radical resection and appropriate histopathologic investigation.     

Wegener granulomatosis: CT and MR findings

PURPOSE: To demonstrate the spectrum of CT and MR imaging findings in patients with Wegener granulomatosis and to determine how often these findings could be attributed to either direct extension from paranasal or orbital disease sites, remote granulomas, or central nervous system (CNS) vasculitis. METHODS: We retrospectively reviewed the CT or MR studies of 15 patients with Wegener granulomatosis. RESULTS: Abnormal findings were seen in 7 patients (5 examined with MR imaging, 2 with CT). Findings included dural thickening and contrast enhancement (3 patients), infarcts (2 patients), regions of hyperintense signal on T2-weighted MR images (2 patients), and abnormal MR signal in the brain stem (2 patients). Three patients with imaging findings of dural enhancement and thickening were thought to have remote granulomatous lesions involving the dura. No patients had extension from sites external to the CNS or clinical findings suggestive of CNS vasculitis. CONCLUSION: The spectrum of CT and MR findings in Wegener granulomatosis includes dural thickening and enhancements cerebral infarction, and MR signal abnormalities in the brain stem and white matter. Presumed remote granulomatous lesions were the most common causes of CNS findings in this study. Complications related to non-CNS disease (eg, hypertension, endocarditis) also appear to have played a role in some patients.     

Cerebral visual impairment in periventricular leukomalacia: MR correlation

PURPOSE: To evaluate the involvement of central visual pathways in cases of periventricular leukomalacia, and to correlate the neuroradiologic findings with the degree of visual acuity. METHODS: The MR brain examinations of 27 preterm children affected by cerebral palsy resulting from periventricular leukomalacia and without significant ophthalmologic lesions were reviewed retrospectively to search for possible involvement of the optic radiations and/or of the calcarine cortex. The data were compared with the degree of visual acuity estimated by means of the Teller Acuity Cards test. RESULTS: Seventeen (63%) of the 27 patients had cerebral visual impairment, which correlated strongly with MR lesions. Quantitative reduction and signal hyperintensity of the peritrigonal white matter and atrophy of the calcarine cortex were present in the more severe cases. In two blind patients, an altered MR signal was detected in the lateral geniculate bodies. CONCLUSION: This study clearly establishes a relationship between specific MR findings and visual impairment in children with periventricular leukomalacia. The finding of hyperintensity in the lateral geniculate bodies was interpreted as an axonal reaction. MR imaging is useful for detecting potential visual impairment and for improving clinical diagnosis.     

Calbindin-D28k is regulated by adrenal steroids in hypothalamic tissue during prenatal development

We report the case of a 42 year-old woman with amyotrophic lateral sclerosis (ALS). Neurological examination showed spastic paraparesis and muscular atrophy of the upper extremities. Increased signal intensity areas were present in the lateral corticospinal tract of the brain and cervical spinal cord on a T2-weighted image. Decreased signal intensity of the motor cortex on the T2-weighted image appeared during the course of the illness. SPECT showed hypoperfusion confined to the motor cortex. The area of increased signal intensity in the cervical spinal cord on the T2-weighted MR images extended to the anterolateral columns of the spinal cord. The area of hypoperfusion in SPECT extended to the fronto-parietal area with the progression of the disease. These changes in the MRI and SPECT findings may reflect progressive degeneration of the upper motor neurons in ALS.     

The low sensitivity of fluid-attenuated inversion-recovery MR in the detection of multiple sclerosis of the spinal cord

PURPOSE: To confirm the expected superiority of fluid-attenuated inversion-recovery (FLAIR) over conventional fast spin-echo MR imaging in the detection of multiple sclerosis (MS) of the spinal cord. METHODS: Fifteen subjects with known MS involving the spinal cord and brain were studied prospectively. The entire cord was imaged with a phased-array coil on a 1.5-T MR system. Sagittal T1-weighted and fast spin-echo proton density- and T2-weighted images were followed by fast FLAIR images. FLAIR parameters were varied to optimize lesion conspicuity with optimal inversion times (TIs) ranging from 2400 to 2600. Lesion conspicuity and detection were compared between the fast spin-echo and FLAIR images by three radiologists who reached agreement by consensus. RESULTS: The FLAIR technique effectively suppressed cerebrospinal fluid (CSF) signal and reduced CSF pulsation and truncation artifacts in all cases. Shorter imaging parameters (repetition time of 4000 to 6000, TI of 1500 to 2000) uniformly decreased lesion conspicuity in all subjects. Of 11 cord lesions in five subjects imaged with the longer parameters (repetition time of 8000 to 11,000, TI of 2400 to 2600), three were not seen on FLAIR images, four were less conspicuous on FLAIR images, and four were seen equally or better on FLAIR images. CONCLUSION: Although successful in suppressing CSF signal and reducing imaging artifacts, fast FLAIR imaging appears unreliable in the detection of MS lesions in the spinal cord.     

Epidural spinal infection. Variability of clinical and magnetic resonance imaging findings

STUDY DESIGN: This study evaluates the magnetic resonance characteristics of spinal epidural abscesses and their associated disc space infections. OBJECTIVES: The results were correlated with history, clinical, and laboratory findings to provide guidelines for early and appropriate diagnosis of epidural spinal infections. SUMMARY OF BACKGROUND DATA: Imaging signs of spinal infections have been reported before, but not with special attention to early clinical and imaging findings. METHODS: Thirteen patients (10 men, 3 women; age range, 32-64 years) with progressive sensorimotor deficit were studied. All patients had a neurologic examination after admission and a magnetic resonance imaging scan done within the first 48 hours. In all cases, T1-weighted images before and after administration of gadolinium were obtained. T2-weighted images were acquired in eight cases as well. Ten patients subsequently underwent open surgery; in three cases, a percutaneous biopsy and drainage was performed. RESULTS: Cervical discitis was found in five patients, and thoracic discitis was seen in another five cases. Three patients had an epidural infection without a concomitant discitis. Neurologic and clinical findings varied considerably. Despite clinical signs of spinal cord involvement, a spinal cord lesion was demonstrated only once. Signal change in T2-weighted images may be the first sign of disc space infection. Because a neurologic deficit may occur before any change is visible, follow-up examinations may be required if epidural infection is suspected on clinical grounds. CONCLUSIONS: Magnetic resonance imaging is the appropriate method for diagnostic work-up of progressive neurologic deficit resulting from epidural infection.     

Contrast enhancement and quantitative signal analysis in MR imaging of multiple myeloma: assessment of focal and diffuse growth patterns in marrow correlated with biopsies and survival rates

OBJECTIVE: This study describes infiltration patterns of multiple myeloma in spinal MR imaging and correlates the findings with biopsies, survival rates, and signal intensity measurements in unenhanced and enhanced studies. MATERIALS AND METHODS: Fifty-three patients with multiple myeloma and 53 age-matched controls underwent MR imaging of the spine. Twenty-nine patients underwent sagittal T1-weighted spin-echo enhanced imaging and all patients underwent sagittal T1-weighted spin-echo unenhanced and opposed-phase gradient-recalled echo images, and signal intensity measurements were taken. MR imaging was correlated to marrow specimens (n = 40) and a clinical staging system. The probability of survival was also calculated. Finally, we performed qualitative visual evaluation (infiltration pattern, degree of tumor involvement) and a quantitative evaluation (marrow signal intensity ratios, contrast enhancement). RESULTS: Five infiltration patterns were found: normal-appearing marrow with low-grade interstitial infiltration (n = 5), focal (n = 18), diffuse (n = 12), focal and diffuse (n = 13), and salt-and-pepper (n = 5). Infiltration pattern correlated with clinical staging; all patients with normal-appearing and salt-and-pepper patterns were clinically stage I. Diffuse marrow infiltration was assessed by marrow ratios: low-grade infiltration, greater than 2.0; intermediate, 1.0-2.0; highgrade, less than 1.0. Contrast enhancement with a signal intensity increase greater than 40% indicated diffuse infiltration. In the control group, all of whom had no marrow disease, enhancement varied (mean +/- SD, 16% +/- 8.9%) but did not exceed 40%. Marrow involvement on MR images correlated significantly with clinical staging and survival (p < or = .001). CONCLUSION: MR imaging with opposed gradient-recalled echo sequences and contrast enhancement provided data that allowed us to classify infiltration patterns and to quantify diffuse marrow involvement in multiple myeloma, both of which correlated to clinical staging and biopsy. Also, the MR data was of prognostic value. Therefore, like laboratory parameters, biopsies, and radiographs, MR imaging can be a supporting pillar in staging and planning treatment of patients with multiple myeloma.     

Congenital ocular motor apraxia: imaging findings

PURPOSE: To determine the frequency of cerebellar and cerebral abnormalities on brain imaging studies in children with congenital ocular motor apraxia. METHODS: Brain imaging studies were performed in 19 children with typical congenital ocular motor apraxia who were in the care of a visual impairment program at a children's hospital. Independent clinical review categorized the subjects as having partial (n = 10) or expanded (n = 9) congenital ocular motor apraxia on the basis of extent of associated speech or neurodevelopmental problems. Fifteen CT studies and 13 MR examinations of the brain performed in these children were reviewed independently by two pediatric neuroradiologists. Radiologic findings were agreed on by consensus. RESULTS: Cerebellar abnormalities were found in 12 of 19 cases. The cerebellar vermis was small in 10 children. A small cerebellar vermis was the only abnormality in five of 10 children with partial congenital ocular motor apraxia and in two of nine children with expanded congenital ocular motor apraxia. Among seven children with a small vermis examined with high-resolution MR imaging, the inferior portion of the vermis was preferentially involved in each case. Of these seven subjects, none of four with partial congenital ocular motor apraxia but two of three with expanded congenital ocular motor apraxia had an abnormality of the superior portion of the vermis. Miscellaneous supratentorial lesions affecting both gray and white matter were found in six subjects. Five of the 19 children had normal imaging findings. CONCLUSION: Inferior vermian hypoplasia is the most common abnormality in children with congenital ocular motor apraxia.     

Clinical and immunological profile of SLE: some unusual features

OBJECTIVE: To study the clinical and immunological profile of children with systemic lupus erythematosus (SLE). DESIGN: Retrospective hospital based study. SETTING: Tertiary level center of North India. SUBJECTS: Sixteen children in the age group 4-12 years. METHODS: Medical records of children with SLE were analyzed. Clinico pathological features were compared with 2 other series from India. RESULTS: Mean age of children at the time of diagnosis was 10 yr and 8 (50%) children were less than 10 yr of age. The female to male ratio was 7:1. Fever (56.2%), rash (87%) and arthritis (87%) were the common clinical manifestations, Renal involvement was noted in 56.2% of cases. Other clinical features included hemolytic anemia (31.2%), thrombocytopenia (18.6%) and Raynaud's phenomenon (12.5%). Cardiac involvement in the form of severe myocarditis and endocarditis occurred in one patient each. Pulmonary hypertension was the presenting feature in one child with right heart failure. One child had multiple sclerosis along with SLE--a rare combination. ANA positivity was seen in all children. Five children died; two had severe cardiac involvement. Three children had renal involvement and one died of pulmonary hypertension. Two-thirds of subjects with renal involvement improved after therapy according to NIH, Bethesda protocol. CONCLUSIONS: SLE must be considered in any child with multisystem disease, as the disease may have certain unusual presentations.     

Reversible signal abnormalities in the hippocampus and neocortex after prolonged seizures

PURPOSE: To investigate the phenomenon of reversible increased signal intensity of medial temporal lobe structures and cerebral neocortex seen on MR images of six patients with recent prolonged seizure activity. METHODS: After excluding patients with known causes of reversible signal abnormalities (such as hypertensive encephalopathy), we retrospectively reviewed the clinical findings and MR studies of six patients whose MR studies showed reversible signal abnormalities. MR pulse sequences included T2-weighted spin-echo coronal views or conventional short-tau inversion-recovery coronal images of the temporal lobes. RESULTS: All six MR studies showed increased signal intensity within the medial temporal lobe, including the hippocampus in five studies. All follow-up MR examinations showed partial or complete resolution of the hyperintensity within the medial temporal lobe and the neocortex. In one patient, results of a brain biopsy revealed severe cerebral cortical gliosis. Temporal lobectomy performed 4 years later showed moderate cortical gliosis and nonspecific hippocampal cell loss and gliosis. CONCLUSION: Significant hyperintensity within the temporal lobe is demonstrable on MR images after prolonged seizure activity, suggestive of seizure-induced edema or gliosis. Damage to medial temporal lobe structures by prolonged seizure activity indicates a possible mechanism of epileptogenic disorders.     

The use of the auditory evoked potential in the diagnosis of multiple sclerosis

Auditory evoked potentials, both early and middle components, were recorded from 227 patients with a variety of conditions including multiple sclerosis, brain stem vascular disease, intracranial tumours and Arnold-Chiari malformation. Abnormalities were found in a substantial proportion of patients with definite multiple sclerosis and a smaller proportion of those in the less definite clinical categories of this condition. There was a high correlation between clinical evidence of brain stem involvement and an abnormal auditory evoked potential in multiple sclerosis. Abnormalities were also found in a few patients presenting with an isolated episode of central nervous system dysfunction involving the brain stem. The auditory evoked potential was abnormal in other patients with known diagnoses including half of those with Arnold-Chiari malformation. Tumours involving the brain stem caused abnormalities of the brain stem evoked potentials in some cases and more frequently distortion of the middle components. The specificity of these auditory evoked potential abnormalities to multiple slcerosis is discussed.     

Complications in Paget disease at MR imaging

PURPOSE: To determine the MR imaging findings in patients with complications of Paget disease of bone. MATERIALS AND METHODS: Of 45 patients with Paget disease who underwent MR imaging, 33 (26 men, seven women; age range, 64-91 years) with known complications of the disease were examined. Imaging in this subgroup included radiography (n = 26), computed tomography (n = 12), bone scintigraphy (n = 15), and magnetic resonance (MR) imaging (n = 33). Patients were examined specifically for musculoskeletal and neurologic complications of Paget disease, including fracture, basilar impression, spinal stenosis, bone tumor, and osteoarthrosis. RESULTS: The 56 complications documented in the 33 patients were fracture (n = 17), neurologic entrapment (n = 19), neoplasm (n = 9), and arthropathy (n = 11). MR imaging was beneficial in the diagnostic evaluation of basilar impression (n = 7), spinal stenosis (n = 12), and the tumor stage (n = 9). It also helped to successfully evaluate pagetic bone narrowing of the coracoacromial arch, which was associated with impingement syndrome and rotator cuff rupture (n = 2). The signal intensities in pagetic bone were most commonly similar to those in fat; this finding had a 100% negative predictive value in excluding neoplasm. CONCLUSION: Although Paget disease is diagnosed economically with conventional radiography, MR imaging is well suited for demonstrating the presence and extent of several characteristic disease complications, including basilar impression, spinal stenosis, and secondary neoplasm.     

Structure and organization of the human uncoupling protein 2 gene and identification of a common biallelic variant in Caucasian and African-American subjects

PURPOSE: We evaluated the intraobserver and interobserver variability in measuring long-term changes in the volume of brain lesions on 5- and 3-mm-thick MR sections in patients with multiple sclerosis. METHODS: Eighteen 18 patients were scanned on two separate occasions with a mean interval of 16.4 months between the two examinations. In each session, a scan with 24 contiguous 5-mm-thick axial sections and another with 40 contiguous 3-mm-thick axial sections was acquired consecutively without moving the patient. We assessed MR lesion load by using a semiautomated local thresholding technique. RESULTS: Lesion volume was significantly higher on images with 3-mm-thick sections than on those with 5-mm-thick sections both at baseline and at follow up. Significant increases in total lesion volume were observed during the follow-up period on images obtained with both 5- and 3-mm-thick sections. The intra- and interobserver variability in measurements of changes in lesion volume was significantly higher on images with 5-mm-thick sections than on those with 3-mm-thick sections. CONCLUSION: Our data indicate that the acquisition of thinner sections increases the reliability of the assessment of changes in brain lesion load on MR images in patients with multiple sclerosis.     

MR of hypoxic encephalopathy in children after near drowning: correlation with quantitative proton MR spectroscopy and clinical outcome

BACKGROUND AND PURPOSE: Quantitative MR spectroscopy has a proved role in the investigation of hypoxia caused by near drowning. To date, no studies have addressed the MR imaging changes that may also accompany this condition. The purpose of this study was to describe the MR imaging findings in children with hypoxic encephalopathy caused by near drowning and to compare these findings with the results of qualitative and quantitative proton MR spectroscopy and clinical outcome. METHODS: Twenty-two children (6 months to 11 years old) admitted to the pediatric intensive care unit after near drowning incidents underwent cerebral MR imaging and quantitative proton MR spectroscopy. Clinical and imaging studies were reviewed retrospectively, and subjects were grouped according to outcome: good result, persistent vegetative state, and death. Images were scored for edema, basal ganglia changes, and cortical changes, and were compared with MR spectra and outcome at days 1 to 2, 3 to 4, and 5 or more. RESULTS: Six patients had a good outcome, four remained in a persistent vegetative state, and 12 died. Generalized/occipital edema correlated with poor outcome. Indistinct lentiform nuclei margins on T1-weighted images were a frequent finding (78%). Basal ganglia T2 hyperintensity correlated with poor outcome, progressing from a patchy/peripheral distribution to diffuse high intensity. Patchy high T2 signal in the cortex or subcortical lines were specific but insensitive for poor outcome, as were brain stem infarcts. CONCLUSION: MR images in children with hypoxic encephalopathy after near drowning show a spectrum of changes. The most sensitive prognostic result may be achieved by combining MR imaging with qualitative and quantitative MR spectroscopic data.     

Optic neuromyelitis: a necrotizing disease of the central nervous system]

Optic neuromyelitis is characterized by simultaneous or successive necrotizing lesions involving the optic nerves and the spinal cord. We report two females with the disease, aged 30 and 34 years old. In the latter, a neuropathological study was done. Both patients had clinical, neuroradiological and pathological features that differed from those of primary demyelinating syndromes such as multiple sclerosis. These patients illustrate the selectivity of optic nerve and spinal cord lesions. The latter involve mainly pyramidal and Goll tracts while, within the necrotizing lesions of the optic chiasma, the fibers of the unaffected optic nerve are spared. This pattern suggests a selective injury to some population of axons. Blood vessels were not affected in the necrotizing areas and the lesions did not follow a vascular territory, therefore a vascular mechanism causing the disease is unlikely. The clinical and neuropathological features of neuromyelitis optic suggest a selective involvement of some axons.     

Serial MR in gene therapy for recurrent glioblastoma: initial experience and work in progress

PURPOSE: To describe the MR imaging findings in a pilot study evaluating gene therapy for treatment of patients with recurrent glioblastoma. METHODS: Serial MR examinations were evaluated retrospectively in patients treated with gene therapy that included a retroviral vector containing the herpes simplex virus thymidine kinase gene and intravenous ganciclovir. Images were obtained after tumor resection and after each cycle of treatment, at approximately 40-day intervals. The volume of enhancing tissue was measured on serial MR images. RESULTS: Eleven patients with recurrent glioblastoma were entered into the clinical trial of gene therapy and seven patients completed at least two cycles of treatment. Of these seven, three patients had an early (between 40 and 80 days) increase in the volume of enhancing tissue followed by a decrease or plateau in enhancing tissue volume. A fourth patient had a stable volume of enhancing tissue for 132 days. The remaining three patients had continuous increases in volume of enhancement on all subsequent MR examinations. CONCLUSION: Although animal data show striking tumor regression in response to similar gene therapy, only limited regression was observed among the seven patients we studied. The transient increases in enhancement seen in three of seven patients might reflect an inflammatory response to local injection of the viral vector.     

Cervical arachnoid cysts after craniocervical decompression for Chiari II malformations: report of three cases

OBJECTIVE AND IMPORTANCE: We describe three cases in which ventrally situated cervical arachnoid cysts led to spinal cord or cervicomedullary compression after repeat craniocervical decompression for Chiari II malformations. CLINICAL PRESENTATION: All three patients underwent craniocervical decompression when their Chiari malformations became symptomatic. The first patient developed chronic vertiginous spells and headache and was treated with repeated craniocervical decompression procedures during several years. Seven months after undergoing her third decompression procedure, she developed severe dizzy spells, which were determined to be of brain stem origin. The second patient had a small, asymptomatic arachnoid cyst anterior to the brain stem discovered at age 6 years. After undergoing repeat craniocervical decompression for headaches 8 years after undergoing his first procedure, the patient developed severe neck pain and acute quadraparesis. A third patient underwent repeat craniocervical decompression at age 14 years for cranial nerve dysfunction. Postoperatively, he acutely developed paresis of extraocular movements and incoordination of the upper extremities. All three patients were found to have anteriorly situated arachnoid cysts compressing the brain stem and/or cervical spinal cord. INTERVENTION AND TECHNIQUE: Fenestration of the arachnoid cyst or drainage with cystoperitoneal shunting adequately treated acute brain stem or cervical spinal cord compression. All three patients had achieved satisfactory relief from their acute symptoms of neural compression at their follow-up examinations. CONCLUSION: An association between spinal arachnoid cysts and neural tube defects has previously been reported. However, the development of previously undetected spinal arachnoid cysts after craniocervical decompression was unexpected. We hypothesize that extensive craniocervical decompression may alter the cerebrospinal fluid pressure dynamics in such a way that the anterior subarachnoid space, previously compressed, may dilate. Occasionally, because of perimedullary arachnoiditis, the cerebrospinal fluid may become loculated and act as a mass. Direct fenestration or shunting may successfully treat this problem, and less extensive craniocervical decompression may avoid it.     

Beneficial effects of acetazolamide on paroxysmal attacks of girdle sensation in multiple sclerosis

A 56-year-old woman with a 40-year history of multiple sclerosis (MS) developed paroxysmal attacks of girdle sensation in the Th5-6 dermatomes. The attacks lasted 20-60 minutes and occured up to three times per week. T2-weighted MR imaging of the spinal cord showed high intensity area from Th5 to Th8. Electrocardiography, echocardiography and laboratory findings did not indicate ischemic heart disease; therefore, the paroxysms were attributed to the spinal cord lesions. Attacks were successfully suppressed by acetazolamide 250 mg/day. Although carbamazepine is frequently used to treat paroxysmal attacks in MS, we would like to suggest that acetazolamide may also be beneficial in some patients with paroxysmal symptoms.     

Comparison of pathological alterations in ALS and a murine transgenic model: pathogenetic implications

The first part of this paper summarizes the main pathological features of sporadic amyotrophic lateral sclerosis (ALS) and familial amyotrophic lateral sclerosis (FALS). In both diseases, the primary lesion consists of degeneration of both upper and lower motor neurons, resulting in severe neuronal loss, particularly in the spinal cord. An important difference between sporadic ALS and FALS is in the involvement of sensory and spinocerebellar projections in the latter. The second part of the paper will compare the familial form of ALS with its recently described transgenic murine model. The production of this model followed the discovery that FALS is tightly linked to several different mutations in the enzyme Cu,Zn superoxide dismutase (SOD), a ubiquitous enzyme involved in the dismutation of superoxide anion to hydrogen peroxide. A human transgene with one of the identified mutations was expressed in mice, and the resulting progeny developed clinical and pathological changes that, in the late stages of disease, were very similar to those in patients with FALS. There was, in fact, exquisite degeneration of motor neurons in spinal cord and brain stem, as well as degeneration of white matter tracts of the spinal cord, of the anterior roots and neurogenic atrophy of skeletal muscles, as described in patients with FALS. Beckman and colleagues postulated that mutations in SOD may alter the structure of the copper active site with resultant decrease in superoxide anion dysmutation while favoring an increase in reactivity with other radicals such as peroxynitrite. The formation of nitronium-like intermediate could damage proteins, particularly by nitration of tyrosine residues. Nitration of tyrosine kinases and altered phosphorilation of neurofilaments could be particularly damaging for motor neurons.