Long term effect of intravenous immunoglobulins and oral cyclophosphamide in multifocal motor neuropathy

Objectives—To report the long term effectof the combined treatment with high dose intravenous immunoglobulins(IVIg) and oral cyclophosphamide (CTX) in patients with multifocalmotor neuropathy, and to determine whether the association of oral CTX in these patients may help to delay and, possibly, suspend IVIg infusions.
METHODS—Six patients with multifocal motorneuropathy responding to an initial course of IVIg (0.4 g/kg/day forfive consecutive days) were followed up for 37 to 61 (mean 47) months.All patients were subsequently treated with periodic IVIg infusions(0.4 g/kg/day for two days at clinical worsening) and oral CTX (1-3 mg/kg/day). Improvement was assessed using the Rankin disability scale,a functional impairment scale for upper and lower limbs, and the MRCrating scale on the 20 most affected muscles. Electrophysiological andantiglycolipid antibody studies were performed before treatment, thenyearly during follow up.
RESULTS—All patients improved during treatmentand, by the end of follow up or before worsening after therapysuspension, the median Rankin (P=0.0335) and upper (P=0.0015) and lowerlimb (P=0.0301) impairment scores and the mean MRC (P=0.0561) scorewere improved. By that time the number of nerves with partial motorconduction block was reduced (P=0.0197) and antiglycolipid antibodytitres had decreased in all but one patient. All patients requiredperiodic IVIg infusions to maintain improvement but, after three toseven months of oral CTX, the interval between IVIg infusions could beprogressively prolonged until, in three patients, both treatments couldbe stopped for up to two years before clinical worsening. The maincomplications, both related to oral CTX, were haemorrhagic cystitis intwo patients and persistent amenorrhea in one patient.
Conclusions—IVIg can induceand maintain improvement in multifocal motor neuropathy but does noteradicate the disease. Oral CTX may help to induce a sustainedremission but it is not devoid of side effects and might therefore bereserved for patients with multifocal motor neuropathy who requirefrequent IVIg infusions to maintain improvement.

     

单纤维肌电图在肌萎缩侧索硬化鉴别诊断中的价值

目的 探讨单纤维肌电图(SFEMG)技术在肌萎缩侧索硬化(ALS)鉴别诊断中的价值.方法 对我院收治的165例ALS患者和145例下运动神经元受累为主的非ALS疾病患者进行伸指总肌SFEMG测定,并测定伸指总肌肌力,按照伸指总肌肌力进行分组,分析不同组之间SFEMG改变的特点.结果 伸指总肌肌力正常者,ALS和非ALS组的平均颤抖(jitter)值分别为(66.1±20.1)、(38.0±9.2)μs(t=9.05),jitter＞55μs的百分比中位数分别为55%、0(Z=-7.81),阻滞所占百分比中位数分别为6.7%、0(Z=-6.93),ALS组各参数均明显高于非ALS组(均P＜0.01).伸指总肌肌力医学研究委员会(MRC)评分≤4者,ALS和非ALS组平均jitter值分别为(93.5±31.2)、(52.8±25.9)μs(t=9.37),jitter＞55μs的百分比中位数分别为86%、20%(Z=-8.46),阻滞所占百分比中位数分别为20%、0(Z=-7.25),ALS组各参数均明显高于非ALS组(均P＜0.01).在MRC评分＞4者,采用平均jitter＞55μ s诊断ALS的敏感性和特异性分别为70.2%和92.7%.结论 当采用SFEMG测定协助ALS的诊断和鉴别时,应尽量选择肌力正常的肌肉.平均jitter、jitter＞55μs的百分比和阻滞在ALS与其他下运动神经元疾病的鉴别诊断中具有重要价值.     

Diencephalic temporal order amnesia.

OBJECTIVE—The neuropathy associated withmonoclonal gammopathy of undetermined significance (MGUS) is typicallya predominantly demyelinating process that may have additional featuresof axonal degeneration. Sixteen patients with MGUS and a pure orpredominantly axonal neuropathy are reported and compared with 20 consecutive patients with demyelinating neuropathy and MGUS who wereseen during the same period.
METHODS—Retrospective review of a consecutiveseries of patients with neuropathy and MGUS evaluated during a fiveyear period.
RESULTS—The axonal group had mild, symmetric,slowly progressive, predominantly sensory neuropathy, usually limitedto the legs. There were no differences in the age of onset or durationof symptoms at the time of presentation, initial symptoms, or theseverity of weakness between the axonal and demyelinating cases.However, the axonal process was associated with less vibration andproprioceptive loss, did not include leg ataxia (present in 55% ofpatients with demyelinating type), less often had generalised areflexia(19% v 70%), IgM gammopathy (19% v 80%),and anti-MAG antibodies (0% v 40%), and had lower CSFprotein concentrations (mean, 49 v 100mg/dl). The illnesswas also generally milder with less disability (mean Rankin score 2.1 v 2.8). Fewer patients with axonal neuropathy improvedwith immunomodulating therapy (27% v 75%).
CONCLUSION—There is an axonal neuropathyassociated with MGUS that is clinically and electrophysiologicallydistinct from the more typical demyelinating pattern.

     

A randomised clinical trial comparing interferon-α and intravenous immunoglobulin in polyneuropathy associated with monoclonal IgM

OBJECTIVES—The polyneuropathy associated with amonoclonal IgM directed to the myelin associated glycoprotein (MAG) isa specific entity with a putative causal link between the IgM and theneuropathy. The small benefit offered by alkylating agents or plasmaexchanges in these patients justifies the search for alternative treatments.
METHODS—A 12 month multicentre, prospective,randomised, open clinical trial was carried out comparing intravenousimmunoglobulin (IVIg; 2g/kg and then 1 g/kg every three weeks) andrecombinant interferon-α (IFN-α; 3 MU/m² subcutaneouslythree times weekly). The main end point was a clinical neuropathydisability score (CNDS) after six months of treatment. Twenty patientswere enrolled; 10 were assigned to IVIg and 10 to IFN-α.
RESULTS—At six months, one out of 10 patientstreated with IVIg had a CNDS improvement of more than 20% whereaseight out of 10 patients treated with IFN-α had such an improvement(P=0.005). The mean CNDS worsened by 2.3 (SD 7.6) (8%) in the IVIggroup whereas it improved by 7.5 (SD 11.1) (31%) in the IFN-α group(P=0.02). This improvement persisted after 12 months and was mainlyrelated to an improvement of the sensory component (P=0.02) whereas themotor component was unchanged (P=0.39). Electrophysiological data did not show improvement of motor nerve conduction velocities whereas sensory nerve conduction velocities improved in the upper limbs. Adecrease in the level of the monoclonal IgM was seen in two patientstreated with IFN-α. At the end of the treatment, antibody activity toMAG was still detected in the serum of all patients.
CONCLUSION—IVIg, as used in this study, did notimprove patients with polyneuropathy and monoclonal IgM. By contrast,although its mechanism of action remains to be fully elucided, IFN-αwas effective in eight out of 10 patients at six months.

     

Neuromuscular disorder as a presenting feature of coeliac disease

OBJECTIVES—To describe the range of neuromusculardisorders which may be associated with cryptic coeliac disease.
METHODS—Nine patients were described withneuromuscular disorders associated with circulating antigliadinantibodies, whose duodenal biopsies later confirmed the diagnosis ofcoeliac disease. Neurological symptoms antedated the diagnosis ofcoeliac disease in all, and most had minimal or no gastrointestinalsymptoms at the onset of the neuromuscular disorder.
RESULTS—Three patients had sensorimotoraxonal peripheral neuropathy, one had axonal motor peripheralneuropathy, one had probable inclusion body myositis and axonal motorperipheral neuropathy, one had polymyositis and sensorimotor peripheralneuropathy, one had mononeuropathy multiplex, one had neuromyotonia,and one had polyneuropathy.
CONCLUSION—A wide range of neuromuscular diseasemay be the presenting feature of coeliac disease. This represents thefirst report of inclusion body myositis and neuromyotonia associatedwith coeliac disease. Estimation of circulating antigliadin antibodiesshould be considered in all patients with neuromuscular disease ofotherwise obscure aetiology.

     

Susceptibility to diabetic neuropathy in patients with insulin dependent diabetes mellitus is associated with a polymorphism at the 5' end of the aldose reductase gene

OBJECTIVES—There is evidence that the polyolpathway is involved in the pathogenesis of diabetic neuropathy. Aldosereductase (ALR2) is the first and rate limiting enzyme of this pathwayand recent studies have suggested that polymorphisms in and around thegene are associated with the development of diabetic microvascular disease. The aim was to examine the role of ALR2 in the susceptibility to diabetic neuropathy in patients with insulin dependent diabetes mellitus (IDDM).
METHODS—One hundred and fifty nine British whitepatients with IDDM and 102 normal healthy controls were studied usingthe polymerase chain reaction to test for a highly polymorphicmicrosatellite marker 2.1 kilobase (kb) upstream of the initiation siteof the ALR2 gene.
RESULTS—Seven alleles were detected (Z-6, Z-4,Z-2, Z, Z+2, Z+4, and Z+6). There was a highly significant decrease inthe frequency of the Z+2 allele in those patients with overt neuropathycompared with those with no neuropathy after 20 years duration ofdiabetes (14.1% v 38.2%, χ² =17.3,p<0.00001). A similar difference was also found between the neuropathygroup and those patients who have had diabetes for< five years with noovert neuropathy (14.1% v 30.2%, χ²=9.0,p<0.0025). The neuropathy group also had a significant decrease in thefrequency of the Z/Z+2 genotype compared with those patients who haveno neuropathy after 20 years duration of diabetes (14.0% v 44.7%, χ²=13.0, p<0.0005).
CONCLUSION—These results suggest that the aldosereductase gene is intimately involved in the pathogenesis of diabetic neuropathy.

     

Neuropathological alterations in diabetic truncal neuropathy: evaluation by skin biopsy

OBJECTIVES—To describe the neuropathologicalfeatures in skin biopsies from patients with diabetic truncal neuropathy.
METHODS—Three patients with diabetic truncalneuropathy underwent skin biopsies from both symptomatic andasymptomatic regions of the chest and trunk. After local anaesthesia,biopsies were performed using a 3 mm diameter punch device (Acupunch).Intraepidermal nerve fibres (IENFs), the most distal processes of smallmyelinated and unmyelinated nerve fibres, were identified afterstaining with PGP 9.5 as previously described.
RESULTS—Diabetes was diagnosed at the time of theneurological presentation in two, and one was a known diabetic patient.All three had associated sensory-motor polyneuropathy. In all, skinbiopsies showed a marked reduction of both epidermal and dermal nervefibres in the symptomatic dermatomes, compared with skin fromasymptomatic truncal areas. In one patient, a follow up skin biopsywhen symptoms had improved showed a return of IENFs.
CONCLUSIONS—In diabetic truncal neuropathy, skinbiopsies from symptomatic regions show a loss of IENFs. After clinicalrecovery, there is a return of the IENF population, suggesting thatimprovement occurs by nerve regeneration. These findings suggest thatsensory nerve fibre injury in diabetic truncal neuropathy is distal to or within the sensory ganglia. Skin biopsy provides a possible tool forunderstanding the pathophysiology of the disease.

     

Decreased β-phenylethylamine in CSF in Parkinson's disease

OBJECTIVE—To determine the concentrations ofβ-phenylethylamine (PEA) in CSF in patients with Parkinson'sdisease, and to evaluate the relation between concentration of PEA inCSF and severity of Parkinson's disease.
METHODS—Using gas chromatography-chemicalionisation mass spectrometry, CSF concentrations of PEA were measuredin 23 patients with Parkinson's disease (mean age, 64.0 (SD 8.2)years), of whom three were at Hoehn and Yahr stage II, 11 were at stageIII, and nine were at stage IV. Comparison was made with eight patientswith neuropathy (mean age, 57.0 (SD 19.2) years) and 12 controlswithout neurological disease (mean age, 57.6 (SD 4.8) years).
RESULTS—Concentrations of PEA in CSF inParkinson's disease were significantly lower (mean 205 (SD 131) pg/ml)than in patients with peripheral neuropathy (433 (SD 254) pg/ml) andcontrols (387 (SD 194) pg/ml). The concentrations of PEA in CSFcorrelated negatively with Hoehn and Yahr stage (P<0.01).
CONCLUSIONS—There are decreased CSF concentrationsof PEA in patients with Parkinson's disease.

     

Single fiber EMG in a congenital myasthenic syndrome associated with facial malformations

Six patients with a newly described genetic syndrome in Iraqi and Iranian Jews of congenital myasthenia associated with facial malformations were studied with voluntary and stimulation single fiber EMG (SFEMG). Voluntary SFEMG revealed abnormal jitter in all patients in both extensor digitorum communis (EDC) and orbicularis oculi (OOC) muscles, though much smaller in the clinically unaffected EDC. SFEMG study of OOC muscle by axonal stimulation at rates from 1 to 48 Hz showed the most increased jitter at the highest stimulation frequencies in the majority of end-plates, one-third of which showed maximal jitter at intermediate rates. These results may suggest a postsynaptic abnormality as the underlying cause for the neuromuscular transmission defect, and demonstrate the usefulness of SFEMG in the diagnosis of congenital myasthenia. © 1993 John Wiley & Sons, Inc.     

Relation between trinucleotide GAA repeat length and sensory neuropathy in Friedreich's ataxia

OBJECTIVE—To verify ifGAA expansion size in Friedreich's ataxia could account for theseverity of sensory neuropathy.
METHODS—Retrospectivestudy of 56 patients with Friedreich'sataxia selected according to homozygosity for GAA expansion andavailability of electrophysiological findings. Orthodromic sensoryconduction velocity in the median nerve was available in all patientsand that of the tibial nerve in 46 of them. Data of sural nerve biopsy and of a morphometric analysis were available in 12 of the selected patients. The sensory action potential amplitude at the wrist (wSAP)and at the medial malleolus (m mal SAP) and the percentage ofmyelinated fibres with diameter larger than 7, 9, and 11 µm in thesural nerve were correlated with disease duration and GAA expansionsize on the shorter (GAA1) and larger (GAA2) expanded allele in eachpair. Pearson's correlation test and stepwise multiple regression wereused for statistical analysis.
RESULTS—A significantinverse correlation between GAA1 size and wSAP, m mal SAP, andpercentage of myelinated fibres was found. Stepwise multiple regressionshowed that GAA1 size significantly affects electrophysiological andmorphometric data, whereas duration of disease has no effect.
Conclusion—Thedata suggest that the severity of the sensory neuropathy is probablygenetically determined and that it is not progressive

     

Application of the MRC brain tumour prognostic index to patients with malignant glioma not managed in randomised control trial

OBJECTIVES—The MRC brain tumour prognostic index,which uses clinical variables to place patients in different outcomecategories, has not been evaluated on a cohort outside a randomisedcontrolled trial. The aims of this study were to (a)determine in a large cohort of patients, derived solely from one centreand not in a clinical trial, whether the MRC prognostic indexstratified patients for outcome; (b) compare actualoutcomes with those obtained in the original studies; and(c) examine whether neuropathological diagnosis was anindependent prognostic variable.
METHODS—The MRC prognostic index was calculatedfor 236 patients with either glioblastoma or anaplastic astrocytomamanaged at a dedicated neuro-oncology clinic in Edinburgh between 1989 and 1995.
RESULTS—For this mixed population of malignantglioma the median survival was 8.6 months. Two year survival was 72.2%for patients with an MRC index score of 1-10; 36.3% for those with anindex score of 11-15; 25.1% for those scoring 16-20; 20.4% withthose scoring 21-25; 4.8% with those scoring 26-33; and 0% forthose scoring 34-38. Exclusion of 79 patients who would not have been eligible for the MRC studies from which the index was derived, becausethey were either too old or did not receive radiotherapy, stillresulted in a similar pattern of stratification but with significantlyimproved median survival times for the lowest two categories.Multivariate analysis of prognostic variables in the Edinburgh cohortshowed that patients with anaplastic astrocytoma did significantlybetter than those with glioblastoma (p<0.001).
CONCLUSIONS—Although there were some differencesin median survival times between the patients in the original MRCstudies and the Edinburgh cohort in similar prognostic categories and atendency to improved two year survivorship in the Edinburgh cohortthese differences have arisen because (a) the Edinburghcohort was accrued about 10 years later than the MRC cohorts and thushad optimal radiotherapy; and (b) many Edinburgh patientswere included in experimental and other chemotherapy studies onrelapse. This study has shown that even outside the setting of aprospective controlled trial and with relaxed inclusion criteria theMedical Research Council (MRC) prognostic index is a robust predictorof outcome in patients with malignant glioma. Survival clearly declinesas the prognostic index increases. Moreover, the prognostic model canbe substantially improved by the addition of histology data, althoughthere is some evidence that this will require complex modelling procedures.

     

Reversal of hypoaesthesia by nerve block, or placebo: a psychologically mediated sign in chronic pseudoneuropathic pain patients

OBJECTIVES—To gainunderstanding of the mechanism and meaning of improvement ofhypoaesthesia after a diagnostic intervention, and of the nature of thepopulation that displays such a sign.
METHODS—Patients withchronic "neuropathic" pain underwent rigorous clinical andlaboratory investigations, including placebo controlled localanaesthetic block. Patients displaying profound regional cutaneoushypoaesthesia and pain entered the study through either of twocriteria: (a) reversal of hypoaesthesiaafter diagnostic block, (b) nerve injury asthe cause of hypoaesthesia and pain. The semeiology displayed by thesepatients together with the behaviour of their sensory phenomena inresponse to blocks were compared. Three groups were expected: (1)patients with "neuropathic" pain with profound hypoaesthesiareversed by block, but without neuropathy; (2) patients whosehypoaesthesia did not reverse and who had neuropathy as the cause oftheir sensory dysfunction; and (3) patients whose hypoaesthesiareversed, and had neuropathy.
RESULTS—Two groupsemerged: (1) patients with profound hypoaesthesia reversed by block,but without neuropathy (27 patients), and (2) patients whosehypoaesthesia did not reverse and who had a neuropathy (13 patients).No patient with neuropathy was found whose cutaneous hypoaesthesiaimproved with block. The first group displayed the sensory-motorcharacteristics of psychogenic pseudoneuropathy. The semeiology of thesecond group was in keeping with organic neuropathy and displayed nopseudoneurological features. Spontaneous pain was relieved by placeboin 66.6% of the patients in group1 and 53.8% in group 2.
CONCLUSIONS—Suchreversal of hypoaesthesia is due to a placebo effect, acting on apsychogenic symptom because: (a) 27 of 27 patients in which the sign occurred had absence of nerve disease behind the "neuropathic" symptoms, (b) In 26 of27 patients the area of hypoaesthesia was non-anatomical, (c) 16 of 27 patients had other sensory-motor signs that could not be explained as aresult of organic pathology (give way weakness and punctual denial of hypoaesthesia), and (d) the phenomenon was not found in patients withorganic neuropathy.

     

Subacute combined degeneration: clinical, electrophysiological, and magnetic resonance imaging findings

OBJECTIVE—Vitamin B₁₂ deficiency is asystemic disease that often affects the nervous system. One of the mostprevalent manifestations is subacute combined degeneration (SCD) of thespinal cord. To access the clinical, electrophysiological, andstructural abnormalities associated with SCD, a study was conducted innine patients.
METHODS—Clinical, electrophysiological(electroneurography, somatosensory and motor evoked potentials), andMRI evaluations were performed in patients before and after treatment.
RESULTS—The most prominent clinical andelectrophysiological findings in all patients were dysfunctions of theposterior column. Corresponding hyperintense lesions in the posteriorcolumn of the spinal cord were found in two patients by T2 weightedMRI. Damage to the central motor pathway was identified in fourpatients. Demyelinating neuropathy was present in one patient andaxonal neuropathy in four. All patients showed improvement of theirsymptoms after treatment with cobalamin. Abnormalities of the spinalcord on MRI disappeared early in recovery. Motor evoked potentials andmedian somatosensory evoked potentials typically normalised aftertreatment, whereas tibial somatosensory evoked potentials remainedabnormal in most patients.
CONCLUSIONS—Clinical, electrophysiological, andMRI findings associated with SCD in vitamin B₁₂ deficiencyare diverse. Thus vitamin B₁₂ deficiency should beconsidered in the differential diagnosis of all spinal cord, peripheralnerve, and neuropsychiatric disorders.

     

Bilateral Horner's syndrome: detection and occurrence

OBJECTIVE—To develop amethod for the detection of bilateral Horner's syndrome in patientswith bilateral interruption of the cervical sympathetic pathway orwidespread autonomic neuropathy.
METHODS—Darknesspupil diameters and redilatation times during light reflexes have beenrecorded with infrared TV pupillometry in 65 healthy subjects, 47 patients with unilateral Horner's syndrome, and 20 patients withbilateral Horner's syndrome. The aetiologies of the last group werediabetic autonomic neuropathy (three cases), amyloidosis (four), pureautonomic failure (PAF) (four), dopamine-β-hydroxylase deficiency(two), and one case each of hereditary sensory and autonomic neuropathy(HSAN) type III, carcinomatous sympathetic neuropathy, familialdysautonomia, multiple system atrophy, Anderson-Fabry disease, andanterior spinal artery thrombosis at C5,6 and one had had bilateralcervical sympathectomies.
RESULTS—Darknessdiameters on the affected side were below normal in 12 patients withunilateral Horner's syndrome, the measurement yielding only 26%sensitivity for detection of the condition. By contrast, the time takento reach three quarter recovery in the light reflex (T_3/4)was abnormally prolonged (redilatation lag) in 33 of the same eyes. Themeasurement yielded 70% sensitivity and 95% specificity for detectionof the condition. In 20 cases, diagnosed on clinical grounds as havingbilateral Horner's syndrome of various aetiologies, pupil diameterswere abnormally small on both sides in five and on one side in threepatients. Fourteen of these patients had significant redilatation lagin both eyes, five patients in one eye, and one patient had it inneither eye. Measurement of redilatation lag was therefore a moresensitive diagnostic test than pupil diameter in both unilateral andbilateral Horner's syndrome.
CONCLUSIONS—Providedthat the pupils are not tonic, bilateral Horner's syndrome can bediagnosed on the basis of redilatation lag. It occurs clinically insome generalised autonomic neuropathies and with interruption of thelocal sympathetic nerve supplies to the two eyes.

     

Chromosome 14 familial Alzheimer's disease: the clinical and neuropathological characteristics of a family with a leucine→serine (L250S) substitution at codon 250 of the presenilin 1 gene

BACKGROUND—Seven affected members aredescribed from a kindred with autosomal dominant familial Alzheimer'sdisease associated with a novel mutation in the presenilin 1 (PS1) geneon chromosome 14that results in a leucine to serine substitution atcodon 250(L250S).
METHOD—Clinical information on the pedigree wascollected directly from family members including affected members andtheir carers and also from hospital records.
RESULTS—Detailed clinical information wasavailable on five members. All had an early age at onset with a medianage of 52 (95% confidence interval (95% CI) 49.4-54.9). Age at onsetvaried between 49 and 56 years, with duration of illness varyingbetween six years and 15 years. Myoclonus, depression, and psychosiswere features of this pedigree; seizures were not reported.
CONCLUSIONS—PS1 L250S familial Alzheimer'sdisease is an early onset form of Alzheimer's disease with clinicalfeatures similar to other reported familial Alzheimer's diseasepedigrees, except that seizures were absent.

     

Poisoning by organophosphorus insecticides and sensory neuropathy

OBJECTIVES—Poisoning by organophosphateinsecticides causes cholinergic toxicity. Organophosphate induceddelayed polyneuropathy (OPIDP) is a sensory-motor distal axonopathywhich usually occurs after ingestion of large doses of certainorganophosphate insecticides and has so far only been reported inpatients with preceding cholinergic toxicity. Surprisingly, it wasrecently reported by other authors that an exclusively sensoryneuropathy developed in eight patients after repeated unquantifiedexposures to chlorpyrifos, which did not cause clear-cut cholinergictoxicity. The objective was to assess whether an exclusively sensoryneuropathy develops in patients severely poisoned by various OPs.
METHODS—Toxicological studies andelectrophysiological measurements were performed in peripheral motorand sensory nerves in 11 patients after acute organophosphate poisoningamong which two subjects were poisoned with chlorpyrifos.
RESULTS—Three patients developed OPIDP, includingone poisoned by chlorpyrifos. Exclusively sensory neuropathy was neverseen after either single or repeated acute organophosphate poisoning. Amild sensory component was associated with a severe motor component intwo of the three cases of OPIDP, the other was an exclusively motor polyneuropathy.
CONCLUSION—A sensory-motor polyneuropathy causedby organophosphate insecticides might occur after a severe poisoningand the sensory component, if present, is milder than the motor one.Bearing in mind the toxicological characteristics of theseorganophosphate insecticides, other causes should be sought for sensoryperipheral neuropathies in patients who did not display severecholinergic toxicity a few weeks before the onset of symptoms and signs.

     

Persistence of tropical ataxic neuropathy in a Nigerian community

OBJECTIVES—The termtropical ataxic neuropathy (TAN) is currently used to describe severalneurological syndromes attributed to toxiconutritional causes. However,TAN was initially proposed to describe a specific neurological syndromeseen predominantly among the Ijebu speaking Yorubas in south westernNigeria. In this study, the prevalence of TAN was determined in Ososa,a semiurban community in south western Nigeria described as endemic forTAN in 1969, and its neurological features were compared withStrachan's syndrome, prisoners of war neuropathy, the epidemicneuropathy in Cuba, and konzo.
METHODS—A census ofOsosa was followed by door to door screening of all subjects aged 10 years and above with a newly designed screening instrument. Subjectswho screened positive had a neurological examination, and the diagnosisof TAN was made if any two or more of bilateral optic atrophy,bilateral neurosensory deafness, sensory gait ataxia, or distalsymmetric sensory polyneuropathy were present.
RESULTS—A total of4583 inhabitants were registered in the census. Of these, 3428 subjectsaged 10 years and above were screened. The diagnosis of TAN was made in206 of 323 subjects who screened positive for TAN. The prevalence ofTAN was 6.0%, 3.9% in males and 7.7% in females. The highest agespecific prevalence was 24% in the 60-69 years age group in women.
CONCLUSION—Theoccurrence of TAN in Ososa continues at a higher prevalence than wasreported 30 years ago. Its neurological features and natural history donot resemble those described for Strachan syndrome, epidemic neuropathyin Cuba, or konzo. The increasing consumption of cassava foods linkedto its causation makes TAN of public health importance in Nigeria, themost populous African country.

     

Guillain-Barré syndrome variants in Emilia-Romagna,Italy, 1992-3: incidence,clinical features,and prognosis

OBJECTIVES—To estimate the incidence rate of Guillain-Barré syndrome variants in an unselected population and to describe their clinical features and prognosis.
METHODS—A two year prospective multicentre study on the incidence and prognosis of Guillain-Barré syndrome was performed in Emilia-Romagna, northern Italy (3 909 512 inhabitants). A surveillance system was instituted within the study area, which comprised all the neurological departments, private and public general hospitals, and practising neurologists. The international classification of diseases (ICD) codes 357.XX (any peripheral neuropathy) of hospital discharges were also reviewed.
RESULTS—Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants. During the study period 18 patients with Guillain-Barré syndrome variants including seven with Miller Fisher syndrome were recruited; the incidence rates were 0.14/100 000/year (95% confidence interval (95% CI) 0.07-0.25) for Guillain-Barré syndrome variants (excluding Miller Fisher syndrome) and 0.09/100 000/year (95% CI 0.04-0.18) for Miller Fisher syndrome. Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases. Death and relapses were not found. Details of clinical, electrophysiological, and CSF findings of Guillain-Barré syndrome variants are provided.
CONCLUSIONS—Guillain-Barré syndrome variants other than Miller Fisher syndrome, as obtained through a population based study, account for about 10% of total cases of Guillain-Barré syndrome and, as a whole, have a good prognosis. Their clinical features are heterogeneous; bifacial weakness (associated with other signs, mainly sensory disturbances) represents the most frequent finding.

     

Carcinoma associated paraneoplastic peripheral neuropathies in patients with and without anti-onconeural antibodies

OBJECTIVE—When tosuspect a paraneoplastic disorder is a puzzling problem that has notrecently been studied in a large series of patients referred forperipheral neuropathy.
METHODS—From 422 consecutive patients with peripheral neuropathy, 26 were analysed whoconcomitantly had carcinoma but no tumorous infiltration, drugtoxicity, or cachexia. Their clinical, pathological, andelectrophysiological data were analysed according to the presence ofanti-onconeural antibodies, the latency between presentation and cancerdiagnosis, and the incidence of carcinoma in the corresponding types ofneuropathy of the population of 422patients.
RESULTS—Seven patients(group I) had anti-onconeural antibodies (six anti-Hu, one anti-CV2)and 19 did not (groups IIA and B). In group I, subacute sensoryneuropathy (SSN) was the most frequent but other neuropathies includingdemyelinating neuropathies were present. Patients in group II A had ashort latency (mean 7.88months), and a rapidly and usually severeneuropathy which corresponded in 11/14 to an established inflammatorydisorder including neuropathy with encephalomyelitis, mononeuritismultiplex, and acute or chronic inflammatory demyelinatingpolyneuropathy (CIDP). Patients in group IIB had a long latency (mean8.4 years) and a very chronic disorder corresponding in four of five toan axonal non-inflammatory polyneuropathy. In this population, theincidence of carcinoma occurring with a short latency was 47% insensory neuronopathy, 1.7% in Guillain-Barré syndrome, 10% inmononeuritis multiplex and CIDP, and 4.5% in axonal polyneuropathy.
CONCLUSIONS—Paraneoplasticneuropathies associated with carcinoma are heterogeneous disorders.Neuropathies occurring with a long latency with tumours probablyresulted from a coincidental association. Neuropathies which occurredwithin a few years of the tumour evolved rapidly and correspondedmostly to inflammatory disorders. As dysimmune neuropathies areprobably paraneoplastic in a limited number of cases, patients withthese disorders should probably not be investigated systematically forcarcinoma in the absence of anti-onconeural antibodies, except when theneuropathy is associated with encephalomyelitis and probably withvasculitis. Questions remain concerning CIDP.

     

Delayed recovery of nerve conduction and vibratory sensibility after ischaemic block in patients with diabetes mellitus

OBJECTIVES—To determine if the recovery of nervefunction after ischaemic block is impaired in patients with diabetesmellitus relative to healthy controls.
METHODS—Median nerve impulse conduction andvibratory thresholds in the same innervation territory were studied inpatients with diabetes mellitus (n = 16) and age matched controls (n = 10) during and after 30 minutes of cuffing of the forearm.
RESULTS—Cuffing caused a 50% reduction of thecompound nerve action potential (CNAP) after 21.9 (SEM 1.6) minutes inpatients with diabetes mellitus and after 10.6 (0.7) minutes incontrols. After release of the cuff the half life for CNAP recovery was5.13 (0.45) minutes in patients with diabetes mellitus and <1 minutein controls. At seven minutes after release of the cuff CNAP was fullyrestored in the controls whereas in patients with diabetes mellitusCNAP had only reached 75.1 (4.1)% of its original amplitude. After onset of ischaemia it took 14.6 (1.9) minutes in patients with diabetesmellitus before the vibratory threshold was doubled, whereas this took5.8 (0.8) minutes in controls. After release of the cuff half time forrecovery of vibratory threshold was 8.8 (1.0) minutes in patients withdiabetes mellitus and 2.6 (0.3) minutes in controls. Ten minutes afterthe cuff was released the threshold was still raised (2.0 (0.3)-fold)in the diabetes mellitus group, whereas it was normalised in controls.Among patients with diabetes mellitus the impaired recovery correlatedwith older age, higher HbA1c, and signs of neuropathy, but not withblood glucose.
CONCLUSION—After ischaemia there is a delayedrecovery of nerve conduction and the vibratory sensibility in patientswith diabetes mellitus. Impaired recovery after ischaemic insults maycontribute to the high frequency of entrapment neuropathy in patientswith diabetes mellitus.