A family with autosomal dominant leukodystrophy linked to 5q23.2-q23.3 without lamin B1 mutations.

BACKGROUND AND PURPOSE: Duplications of lamin B1 (LMNB1) at 5q23 are implicated in adult-onset autosomal dominant leukodystrophy (ADLD) having been described in six families with diverse ethnic background but with a homogeneous phenotype. In a large Italian family, we recently identified a variant form of ADLD characterized clinically by absence of the autonomic dysfunction at onset described in ADLD and, on MRI, by milder cerebellar involvement with sparing of hemispheric white matter. Aim of this study was to investigate the genetic basis of this variant form of ADLD. METHODS: We carried out a genome-wide linkage analysis using microsatellite markers, and the genes in the candidate region were screened for point mutations. LMNB1 was also screened for deletions/duplications by real-time PCR, multiplex ligation-dependent probe amplification and Southern blot. RESULTS: We mapped the variant ADLD locus to 5q23.2-q23.3, a genomic region containing 11 genes including LMNB1. Neither gene copy-number defects nor point mutations in the LMNB1 gene were found. We also excluded point mutations in the coding exons of the other ten genes in the candidate region. However, expression of lamin B1 evaluated in lymphoblastoid cells was higher in patients than in healthy controls, and was similar to the lamin B1 expression levels found in a patient with LMNB1 duplication. CONCLUSIONS: This observation suggests that a mutation in an LMNB1 regulatory sequence underlies the variant ADLD phenotype. Thus, adult forms of ADLD linked to 5q23 appear to be more heterogeneous clinically and genetically than previously thought.

Considerations about Occlusion of the Intracranial Distal Internal Carotid Artery.

Occlusion of the intracranial distal internal carotid artery (ICA) is one of the most critical conditions among the cases of acute stroke in the anterior circulation. The introduction of selective endovascular treatment first using thrombolytic agents replaced later by the mechanical thrombectomy using various devices has improved the prognosis in a certain number of these patients. Among the factors influencing the prognosis of these patients, one is the collateral circulation which in these cases is mainly characterized by leptomeningeal anastomoses. The collateral can, however, be impaired, by distal embolization and by anomalies of the Circle of Willis: the aim of this study is to describe these aspects.

Chronic systemic high-dose recombinant interferon alfa-2a reduces exacerbation rate, MRI signs of disease activity, and lymphocyte interferon gamma production in relapsing-remitting multiple sclerosis.

We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.

Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment.

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.

Propofol analgesia in central pain: preliminary clinical observations.

Propofol, an intravenous general anaesthetic, has been reported to relieve some forms of pruritus at subhypnotic doses. We assessed its effectiveness in 32 patients with several kinds of non-malignant chronic pain, in a placebo-controlled, double-blind study. We found that central pain, but not neuropathic pain, is at least partially controlled by propofol at subhypnotic doses, without major side-effects. In particular, allodynia associated with central, but no neuropathic, pain has been completely controlled. Propofol analgesia leads to renormalization of brain metabolism as seen on single photon emission computed tomography. We conclude that propofol may help in the diagnosis of central pain, particularly in unclear cases, and also in treatment. Possible mechanisms of action are discussed.

Transforming growth factor beta1 (TGFbeta1) mRNA level correlates with magnetic resonance imaging disease activity in multiple sclerosis patients.

Eight relapsing-remitting multiple sclerosis (MS) patients were tested for the level of transforming growth factor beta1 (TGFbeta1) mRNA in peripheral blood mononuclear cells every 15 days for 6 months. Disease activity was evaluated every 4 weeks by magnetic resonance imaging (MRI) and neurological examination. An inverse correlation was found between the level of TGFbeta1 mRNA and MRI disease activity. The level of TGFbeta1 mRNA predicted the presence of disease activity in the scans performed 2-4 weeks later with high sensitivity (88%) and specificity (87.5%) suggesting that TGFbeta1 mRNA quantification could be an indicator of disease activity in MS.

Uncommon symptomatic cerebral vascular malformations.

We describe three cases of unusual vascular malformations in which the most relevant angiographic findings were the presence of a pathologic arteriovenous shunt through multiple small direct arteriovenous fistulas and the lack of a clearly identifiable nidus. All malformations were symptomatic. Such lesions are relatively rare, but they should be taken into consideration in the differential diagnosis of cerebrovascular malformations.

Superficial siderosis of the CNS: MR diagnosis and clinical findings.

PURPOSE: To report the clinical and neuroradiologic findings of superficial siderosis of the CNS, due to chronic subarachnoid bleeding of unknown origin. MATERIALS AND METHODS: We observed seven cases. The main clinical manifestations were progressive deafness and ataxia. Four patients had had previous cranial or cervical trauma, with root avulsion in two, many years before onset of deafness and ataxia. Neuroradiologic studies included MR (0.5 T in four and 1.5 T in three) and angiography of the brain in all cases, CT in six cases, MR of the spine in six, and myelography in four. RESULTS: MR demonstrated a rim of marked hypointensity in T2-weighted images, consistent with hemosiderin deposits, on the surface of cerebellum, brain stem, inferior part of cerebral hemispheres, and spinal cord. CT showed cerebellar atrophy in five cases, and a rim of mild hyperdensity around the brain stem in two. Angiographic studies were negative. Myelography showed cervical nerve root avulsion in two cases and a cervicodorsal extradural cyst in one. Cerebrospinal fluid contained RBCs in all the six examined cases. CONCLUSION: Although CT may occasionally suggest the diagnosis of superficial siderosis, MR demonstrates this abnormality to better advantage.

PCV chemotherapy for recurrent oligodendrogliomas and oligoastrocytomas.

OBJECTIVE: The role of chemotherapy in the treatment of low-grade oligodendrogliomas and oligoastrocytomas is still unclear. A Phase II study was conducted to determine the benefits and toxicity of the procarbazine, lomustine, and vincristine (PCV) regimen in patients with low-grade oligodendrogliomas and oligoastrocytomas recurrent after surgery alone or surgery with radiotherapy. METHODS: Patients with both enhancing and nonenhancing tumors were treated with up to six cycles of standard PCV, and response was evaluated by conventional criteria based on computed tomography or magnetic resonance imaging. RESULTS: Sixteen of 26 patients (62%) responded to PCV: 3 (12%) experienced complete response, 13 (50%) experienced partial response, 8 (31%) had stable disease, and 2 (8%) had progressive disease. All symptomatic patients who responded and three with stable disease improved in seizure frequency, lateralizing signs, and symptoms of intracranial hypertension. The response rate for patients with enhancing lesions revealed by computed tomography or magnetic resonance imaging (74%) was significantly higher than that of patients with nonenhancing lesions (29%) (P < 0.05). Both oligodendrogliomas and oligoastrocytomas responded to PCV, with complete responses occurring in association with pure tumors only. The median time to tumor progression of all 26 patients was 24 months and was significantly longer for those with oligodendrogliomas compared with those with oligoastrocytomas (32 versus 12 mo) (P < 0.001). Chemotherapy was well tolerated, with mild hematological toxicity and rare skin rashes being the most frequent sequelae. CONCLUSION: These results suggest that chemotherapy with PCV is effective in the treatment of recurrent low-grade oligodendrogliomas and oligoastrocytomas.

Traumatic exophthalmos due to an uncommon arteriovenous fistula without involvement of the cavernous sinus. Case report.

A case of traumatic exophthalmos due to an arteriovenous fistula between the middle meningeal artery and the veins at the base of the skull is reported. There was no involvement of the cavernous sinus. Embolization following selective transfemoral catheterization of the external carotid artery resulted in complete relief of the symptoms.

[Routine use of a catheter technique for cerebral angiography (965 examinations) (author's transl)]. / Bericht über die routinemäbige Anwendung der Kathetertechnik in der zerebralen Angiographie (965 Untersuchungen)

The authors report their experience with routine use of a catheter technique for cerebral angiography. The complication rate is low and the diagnostic yield is increased. They conclude that it is superior to direct puncture of the vessels in the neck and to retrograde brachial angiography.

[Computer tomography and spinal angiography in the diagnosis of spinal angioma]. / Ein Beitrag der Computertomographie und der spinalen Angiographie zur Diagnostik eines Wirbelangioms.

The computer tomographic and angiographic features of spinal angiomas are described. The authors observed 21 cases and, on the basis of this material, they deal with the clinical features, radiological appearances, disease patterns, forms of treatment, and prognosis. CT and angiography produce a fairly uniform and typical appearance, permitting diagnosis before therapy. Problems in differential diagnosis and errors in interpretation are enumerated.

[Radiogenic carotid stenosis. The problem of radiation induced arterio-sclerosis (author's transl)]. / Radiogene Karotisstenose. Zum Problem der strahleninduzierten Arteriosklerose

Amongst late radiation damage, lesions of the cerebral arteries are relatively rare. The relationship between the radiation and arterio-sclerosis is discussed in connection with a 63-year old female patient with an atheromatous carotid stenosis; at the age of 5 years she received high dose rate radiation for cervical node tuberculosis. From animal experiments and an increasing number of human observations, it is concluded that radiation may be a predisposing and accelerating local factor in the formation of arterio-sclerosis. Amongst the recognised cases of radiogenic carotid stenosis or occlusion, the latent period averages 30 (9-57) years.

Spinal intramedullary cavernous angiomas: a literature meta-analysis.

The present report reviews 57 (out of 65) cases of spinal intramedullary cavernomas collected from the literature, plus one personal patient. Almost 70% of all patients were women. Mean age at diagnosis for women was 36.4 years, with a peak in the third decade. More than three-fourths of all women became symptomatic between the second and fourth decades, with a peak in the fourth decade. Unlike in men, cervical and thoracic lesions are almost equally represented, generally involving 1-2 vertebral levels. Mean size at diagnosis is 1.7 cm; no enlargement over time was seen. Symptoms are more frequently acute; pain and sensorimotor deficits are the usual complaints, but the clinical picture may simulate that of multiple sclerosis. The duration of history was less than 5 years in more than 80% of women. Bleeding was seen in 60% of women, with a risk of 1.6%/person-year of exposure globally. Cervical lesions have both a shorter course and increased frequency of bleeding. If not immediately recognized, repeated cycles of bleeding are the norm, with a mean interval of 39.6 months between the first and second episodes. The preoperative status was the single most important factor bearing on outcome, whereas sex, age, size, location, duration of history and extent of removal were not. Magnetic resonance imaging was diagnostic in all cases, whereas angiography was 100% negative. Surgery should not be a necessary first option, as recovery from the first bleeding is apparently fairly frequent.

Primitive cerebral melanoma: case report and review of the literature.

BACKGROUND: Central nervous system primary malignant melanoma accounts for approximately 1% of all the cases of melanoma; reports in the literature are relatively rare. CASE DESCRIPTION: A 74-year-old man was hospitalized because of an episode of aphasia. The neuroradiologic examinations demonstrated a round homogeneous lesion extending near the left sylvian fissure. He had no extracranial abnormalities. The patient underwent a neurosurgical procedure and the tumor was macroscopically totally excised. Pathological examination of the surgical specimen revealed a histological appearance similar to that of melanoma. A diagnosis of primary CNS melanoma was made after careful dermatologic and ophthalmologic examination, which ruled out presence of cutaneous or choroidal melanoma. The patient did not receive any further treatment and he is free of disease 2 years after diagnosis. CONCLUSIONS: We report a case of primary cerebral melanoma of the left temporal lobe; clinical, neuroradiological, and histological findings are discussed with review of the literature. Primary melanoma of the CNS may present either with localized intra/extra-axial mass lesions or with meningeal spread, which carries a worse prognosis. The prognosis of cerebral primitive melanoma is variable, although it is common opinion that primitive cerebral melanoma has a better prognosis than cutaneous melanoma, with two cases in the literature surviving 9 and 12 years.

[Neurotoxic action of muzolimine at high doses in uremic patients. Observation of a group of 29 subjects]. / Azione neurotossica della muzolimina ad alte dosi in pazienti uremici. Osservazione su un gruppo di 29 soggetti.

We report the results of a study on 29 patients affected by renal chronic insufficiency and treated with high doses of muzolimine. From our data it results that to the muzolimine is probable due a neurological syndrome very similar to combined sclerosis. Up today, it is not possible to know how and where the muzolimine develops its neurotoxic effect.

Primary cerebellar and spino-cerebellar ataxia an MRI study on 63 cases.

63 patients with primary cerebellar and spinocerebellar ataxia have been studied with MRI. This method allows to identify in vivo different groups of diseases such as that characterized by atrophy of cerebellum alone; that with atrophy of cerebellum associated with brainstem changes; the forms with associated changes of basal ganglia; the forms with spinal cord atrophy alone, as well as transitional forms. An interesting correlation between the varying groups and the type of inheritance was found, while no correlation with other clinical aspects was observed.

Spontaneous ICA dissection presenting with 12th nerve palsy. Clinical and radiological considerations.

Three cases of 12th nerve palsy due to dissection of the ICA are reported. The clinical and radiological features are described. The useful role played by MRI in the diagnosis is emphasised.

[Spontaneous dissection of the internal carotid artery with 12th nerve palsy. Radiologic and clinical aspects]. / Dissection spontanée de la carotide interne avec paralysie du XII. Aspects cliniques et radiologiques.

Three cases of 12th nerve palsy due to dissection of the ICA are reported. The clinical and radiological features are described. The useful role played by MRI in the diagnosis is emphasised.