A. Lugaresi

Fatal Familial Insomnia and Dysautonomia with Selective Degeneration of Thalamic Nuclei

The thalamus is affected in diffuse degenerative processes of the nervous system.1 2 3 4 5 However, it has not been established whether a genetically determined degenerative disease may be limited ...

Autologous hematopoietic stem cell transplantation suppresses Gd-enhanced MRI activity in MS.

Background: Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS. Objective: To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety. Methods: In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months. Results: The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable. Conclusion: These results demonstrate that the therapeutic sequence CY–BEAM–ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Acute motor conduction block neuropathy Another Guillain–Barré syndrome variant

To the Editor: We read with interest the recent article by Isayev et al.1 They describe three cases of ischemic stroke in young adults that occurred during or after air travel. All patients were diagnosed with a patent foramen ovale (PFO) and no other plausible cause of stroke could be found, suggesting the existence of an “economy class stroke syndrome.” To underscore the importance of their report, we would like to add three very similar patients (aged 21, 63, and 64 years) with otherwise unexplained ischemic strokes that occurred during long-distance air travel ( 9000 km in each case) who were admitted to our department within the last year. All patients developed their symptoms toward the end of their flights, one patient immediately following a prolonged defecation with repeated Valsalva maneuvers. All infarcts appeared embolic upon brain imaging. They were located in the right middle cerebral artery territory in one patient and in the posterior thalamus with transient “top of the basilar” syndrome in another. The third patient had multiple embolic cerebral infarctions accompanied by fulminant pulmonary embolism. The latter patient carried a homozygote prothrombin gene G20210a mutation and subsequently died due to cerebral herniation. The other two patients recovered with no or minimal residual deficits. All patients had a PFO as demonstrated by transesophageal echocardiography; one patient had an additional intraseptal aneurysm. Similar to the patients reported by Isayev et al. lower limb venous Doppler performed within 1 to 3 days after the events was negative in all three cases, as were their extracranial and intracranial Doppler/duplex examinations, ECG-Holter recordings, and all other coagulation studies (antithrombin, Factor V Leiden mutation, anticardiolipin antibodies, lupus anticoagulant, proteins C and S). Although two of our patients were in their 60s, none of them showed evidence of atherosclerosis or other cardiovascular risk factors. Of course, due to the worldwide increase of air travel activities, more people will have a stroke in flight by mere chance. We also assume that embolic strokes during or due to long-distance air travel have been underreported in the literature, but one more patient was reported a few years ago in a French journal.2 Until more systematic investigations become available, ischemic stroke should be included in the list of potential complications of longdistance air travel, especially in the presence of PFO.

Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy

OBJECTIVE It is important to recognize CIDP occurring in diabetics because, unlike diabetic polyneuropathy, it is treatable. The aim of this study was to find out whether there are clues which help to differentiate CIDP in diabetics from diabetic polyneuropathy. METHODS We compared the electrophysiological and pathological findings of 7 diabetics, who developed a predominantly motor polyneuropathy with the features of CIDP, with a group of diabetics referred for symptomatic polyneuropathy. RESULTS Of the 7 diabetics we believe developed CIDP, 6 met at least 3 and one patient two of the 4 electrophysiological criteria of demyelination. Of the 100 patients referred for diabetic polyneuropathy, only 4 fulfilled two criteria and none 3. Nerve biopsy findings were not helpful in differential diagnosis, as segmental demyelination and remyelination, onion bulbs and inflammatory infiltrates, which are the histologic features of CIDP, were also present in diabetic polyneuropathy. CONCLUSIONS CIDP can be diagnosed in a diabetic patient when motor symptoms are predominant, are more severe than expected in diabetic polyneuropathy and 3 of the 4 electrophysiological criteria for demyelination are fulfilled. When only two criteria are met, we believe that a trial with one of the established treatments for CIDP may be helpful in confirming the diagnosis.

Anti-sulfatide antibodies in neurological disease: binding to rat dorsal root ganglia neurons

Increased titers of anti-sulfatide antibodies were detected by ELISA in 5 of 200 patients and control subjects. All 5 patients had sensory impairment; 4 had neuropathy, and one had multiple sclerosis. Of the patients with neuropathy, 2 had a clinical syndrome of small fiber sensory neuropathy with normal electrophysiological or nerve biopsy studies, 1 had a sensorimotor axonal neuropathy associated with IgM monoclonal gammopathy, and 1 had sensorimotor neuropathy with multifocal motor conduction block and anti-GM1 antibodies. The anti-sulfatide antibodies bound to the surface of unfixed rat dorsal root ganglia neurons and human neuroblastoma cells, and to fixed sections of central and peripheral myelin. No binding was detected following intraneural injection into rat sciatic nerves. Pre-absorption with sulfatide but not with galactocerebroside eliminated the tissue binding activity. These findings indicate that increased titers of anti-sulfatide antibodies are found in patients with sensory impairment but are not restricted to a particular neurological syndrome or type of neuropathy. The significance of anti-sulfatide antibodies is uncertain although sulfatide on dorsal root ganglia neurons may be a target antigen.

Apolipoprotein E genotype does not influence the progression of multiple sclerosis

Abstract.Objective:To investigate the association between apolipoprotein E (APOE) polymorphisms and the progression of MS.Methods:We investigated 428 subjects affected by clinically defined MS, with a disease duration of at least three years. We collected data concerning the age at onset of MS, clinical type, disease duration and disability according to the expanded disability status scale (EDSS). We also calculated the progression index (PI) to evaluate disease progression. APOE genotyping and the –491 A/T polymorphism of the APOE promoter were determined.Results:No association was observed between the APOE ε4 allele and clinical characteristics of our study population. We also investigated the –491 A/T APOE promoter polymorphism in 236 MS subjects and did not find any association between the –491 A/T polymorphism and the selected clinical variables.Conclusions:In our population the APOE ε4 allele and the –491 A/T APOE promoter polymorphism are not associated with a more rapid course of MS.

Psychic akinesia following carbon monoxide poisoning

In 3 patients, carbon monoxide poisoning was followed by a modification of habits and personality without definite mental deterioration, but with loss of initiative, which led the patients to lose all their previous interests and to spend most of their time in bed. CT scans showed bilateral calcification of globi pallidi in one patient and pallidal hypodensities in another.

Anti-GD1a antibodies from an acute motor axonal neuropathy patient selectively bind to motor nerve fiber nodes of Ranvier

Acute motor axonal neuropathy (AMAN) is associated with high titer anti-GD1a antibodies. We have found that very high titer IgG anti-GD1a antibodies (Ab) from one AMAN patient selectively bind to motor, but not sensory, nerve nodes of Ranvier. Binding is abolished by preadsorption with GD1a. Sera negative for Ab do not immunostain motor and sensory nerve roots. We have also found that botulinum toxin A (BTA), which binds to GD1a, stains both motor and sensory nerve nodes of Ranvier. Our results strongly support the pathogenetic role of anti-GD1a antibodies in AMAN. Why BTA also binds to sensory fibers still remains to be elucidated, although the different size of BTA and its specificity to other gangliosides present in sensory axons might represent important factors.

Benign monomelic amyotrophy of lower limb: a rare entity with a characteristic muscular CT.

Six patients presented with amyotrophy confined to a single lower limb and characterized by insidious onset, slow progression and later stabilization. Wasting was out of proportion with disability and there were no sensory, pyramidal tract or bulbar signs. All cases were sporadic, and there was no history of poliomyelitis. CK, anti-ganglioside antibodies, motor and sensory conductions were normal. Quantitative EMG and muscle biopsy revealed neurogenic features also in clinically unaffected limbs. Muscular CT showed selective or predominant, asymmetrical involvement of posterior leg muscles and caput longus of biceps femoris. Monomelic amyotrophy of lower limb is a clinically localized variant of spinal muscular atrophy with a particularly benign course. Although in the early stage there are no clinical or laboratory findings which allow differential diagnosis with other motor neuron diseases, the history of an amyotrophy clinically localized for more than 3 years to a lower single limb and the characteristic muscular CT pattern suggest the diagnosis since the first observation and indicate a favorable prognosis.

Low-dose oral methotrexate treatment in chronic progressive multiple sclerosis.

Abstract. We aimed to further assess the safety and efficacy of low-dose oral methotrexate (LDOM) treatment for chronic progressive MS (CPMS). We studied 20 CPMS patients, including 16 with secondary progressive MS who had shown disease progression in the previous year. The mean follow-up was 23 months. The mean EDSS score was 6.3 ± 1.1 before treatment and 6.4 ± 1.1 after one year of treatment. At one year, 15 of 20 patients were still being treated, and 10 were stable. Twelve patients have completed 18 months of treatment, and eight are stable. Two patients stopped treatment because of side effects, two more because they did not perceive benefit, and one was lost to follow-up. Six patients had mild, transient increases in liver enzymes not requiring treatment interruption, and two had localized herpes zoster. Magnetic resonance imaging (MRI) performed before treatment and at one year remained unchanged in responders. We confirm that LDOM is safe in carefully selected and monitored CPMS patients. MTX is inexpensive and, given its anti-inflammatory and immunomodulatory properties, may be used as add-on therapy in non-responders to interferon beta, although hepatic toxicity may be a problem in long-term treatment.