Subcutaneous immunoglobulin as first-line therapy in treatment-naive patients with chronic inflammatory demyelinating polyneuropathy: randomized controlled trial study.

BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is effective as maintenance treatment in chronic inflammatory demyelinating polyneuropathy (CIDP). We investigated whether multiple subcutaneous infusions are as effective as conventional therapy with intravenous loading doses in treatment-naive patients with CIDP. METHODS: Twenty patients fulfilling the clinical and electrophysiological criteria for CIDP were included and treated with either SCIG (0.4 g/kg/week) for 5 weeks or intravenous immunoglobulin (IVIG) (0.4 g/kg/day) for 5 days. After 10 weeks, patients were switched to the opposite treatment arm and followed for a further 10 weeks. All participants were evaluated at weeks 0, 2, 5 and 10 during both therapies. Primary outcome was combined isokinetic muscle strength (cIKS). Secondary outcomes were disability, clinical evaluation of muscle strength and the performance of various function tests. RESULTS: All participants received both therapies, 14 completing the protocol. Overall, cIKS increased by 7.4 ± 14.5% (P = 0.0003) during SCIG and by 6.9 ± 16.8% (P = 0.002) during IVIG, the effect being similar (P = 0.80). Improvement of cIKS peaked 2 weeks after IVIG and 5 weeks after SCIG. Disability improved during SCIG treatment only. Muscle strength determined by manual muscle testing improved after 5 and 10 weeks during SCIG but only after 5 weeks during IVIG. The remaining parameters improved equally during both treatments. Plasma immunoglobulin G levels at baseline and improvement of cIKS were related. CONCLUSION: In treatment-naive patients with CIDP, short-lasting SCIG and IVIG therapy improve motor performance to a similar degree, but with earlier maximal improvement following IVIG than SCIG treatment.

Subcutaneous immunoglobulin in responders to intravenous therapy with chronic inflammatory demyelinating polyradiculoneuropathy.

BACKGROUND AND PURPOSE: We hypothesized that subcutaneous administration of immunoglobulins (SCIG) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is feasible, safe and superior to treatment with saline for the performance of muscle strength. METHODS: Thirty patients with motor involvement in maintenance therapy with intravenous immunoglobulin (IVIG) fulfilling the EFNS/PNS criteria for CIDP, aged 18-80 years, were randomized either to SCIG at a dose corresponding to their pre-study IVIG dose or to subcutaneous saline given twice or thrice weekly for 12 weeks at home. At the start and end of the trial as well as 2 weeks before (-2, 0, 10, 12 weeks), isokinetic strength performance of four predetermined and weakened muscle groups was measured. Also, an Overall Disability Sum Score (ODSS), 40-m-walking test (40-MWT), nine-hole-peg test, Neurological Impairment Score (NIS), Medical Research Council (MRC) score, grip strength, standardized electrophysiological recordings from three nerves, and plasma IgG levels were evaluated. RESULTS: SCIG treatment was well tolerated in all 14 patients. Six patients complained of mild side-effects at the injection site. In the SCIG group there was an increase of isokinetic muscle strength of 5.5 ± 9.5% (P < 0.05) as compared with a decline of 14.4 ± 20.3% (P < 0.05) in the placebo group; the difference between the two groups being significant (P < 0.01). ODSS, NIS, MRC, grip strength and 40-MWT improved following SCIG versus saline. CONCLUSIONS: SCIG treatment in CIDP is feasible, safe and effective, and seems an attractive alternative to IVIG.

Radiation-induced brachial plexopathy: neurological follow-up in 161 recurrence-free breast cancer patients.

PURPOSE: The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients, treated according to the Danish Breast Cancer Cooperative Group protocols. METHODS AND MATERIALS: One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months (13-99 months). After total mastectomy and axillary node sampling, high-risk patients were randomized to adjuvant therapy. One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks. In addition, 82 of these patients received cytotoxic therapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and 46 received tamoxifen. RESULTS: Five percent and 9% of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy, respectively. Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy (p = 0.04) and in younger patients (p = 0.04). The clinical manifestations were paraesthesia (100%), hypaesthesia (74%), weakness (58%), decreased muscle stretch reflexes (47%), and pain (47%). CONCLUSION: The brachial plexus is more vulnerable to large fraction size. Fractions of 2 Gy or less are advisable. Cytotoxic therapy adds to the damaging effect of radiotherapy. Peripheral nerves in younger patients seems more vulnerable. Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus.

Inter-observer variation in the evaluation of neurological signs: patient-related factors.

The influence of patient-related factors on inter-observer variability in the evaluation of neurological signs was investigated. Two hundred and two consecutive unselected inpatients were examined by two senior neurologists who were unaware of the neurological case history. Eight signs were evaluated: anisocoria, jerky eye movements, facial palsy, difference in elbow extension force, abnormal finger-nose test, Barré sign, difference in knee jerk, and extensor plantar reflex. Agreement rates were calculated in order to compare the inter-observer variability with reference to the patients' sex, age, mode of admission, and diagnosis at discharge. Observed agreement rates for the eight examined signs only sporadically showed statistically significant differences between the chosen patient-related factors. In general, inter-observer variation does not appear to be influenced by the sex, age, mode of admission or diagnosis at discharge of the patients.

[Myotonic dystrophy. Genetic, neonatologic and neuropsychological aspects]. / Dystrophia myotonica. Genetiske, neonatologiske og neuropsykologiske aspekter.

Dystrophia myotonica (DM) is an autosomally dominant hereditary multi-organ disease which is characterized primarily by myotonia and muscular atrophy and thereafter by cataract and disturbances in cardiac conduction. The prevalence is stated to be 2.5-5.5 per 100,000. The disease may be manifest at birth or may become manifest later, right up to the age of 60-70 years, on an average about the age of 20 years. The earlier the commencement of the disease, the more severe the course and the condition becomes crippling. The survival is reduced on an average by 25 years. The diagnosis is based on the clinical findings, information about familial occurrence of DM, electromyography and split lamp examination. The penetration of the DM gene is practically 100% by the age of 14 years but the expression varies greatly. By examination of chorion villi in informative families it will be possible to predict with 96-98% probability whether an embryo will develop DM or not. Genetic research in recent years has rendered prenatal diagnosis possible and diagnosis of the DM gene prior to conception in clinically healthy family members. No specific treatment is available.

[Brachial irradiation plexopathy]. / Brakial strålepleksopati.

Irradiation neuropathy is a term for the damage to peripheral nerve tissue due to irradiation. Brachial irradiation plexopathy is irradiation neuropathy affecting the brachial plexus. This is most frequently a complication of irradiation therapy for cancer of the breast. The incidence varies considerably and is lowest with low total doses of irradiation and limited fractions. The latent period varies from months to several years. The neurological manifestations are paraesthesiae in the fingers, pain, hypaesthesia, hypalgesia, disaesthesia, paresis, hyporeflexia, muscular atrophy and possibly vegetative disturbances. Horner's syndrome may occur. Lymphoedema is observed in approximately on third of the patients. The course of brachial irradiation plexopathy is progressive. No specific treatment is available. The diagnosis is based on the case history, clinical picture, electrodiagnosis and CT of the brachial plexus region. The most important differential diagnosis is metastatic infiltration in the brachial plexus. These two conditions are differentiated best by means of CT guided surgical exploration and histological examination of the tissue. The irreversible nature of brachial irradiation plexopathy and its marked resistance to treatment are such that the optimal irradiation hygienic rules must be observed.

[Klippel-Trenaunay-Weber syndrome. Magnetic resonance imaging diagnosis of medullary involvement]. / Klippel-Trenaunay-Weber-syndrom. Magnetisk resonans billeddiagnostik ved medullaer affektion.

The Klippel-Trenaunay-Weber (KTW) syndrome is a rare congenital syndrome of unknown etiology consisting of the triad: a large cutaneous naevus, congenital varicosities and hypertrophy of bones and soft tissues. A heterogenous group of vascular malformations may also occur. The case record of acute myelopathy in a patient aged 42 years with recognized KTW syndrome is presented. It is concluded that magnetic resonance imaging is indicated in cases of suspected intramedullary haemorrhage in patients with congenital vascular malformations.

[Intrathecal distribution of iohexol after cervical myelography]. / Intratekal iohexolfordeling efter cervikal myelografi.

Cervical myelography was performed in fourteen patients under suspicion of cervical disc herniation. Prior to myelography, complete cranial-CT registration of the density in the subarachnoid space, intraventricularly, subcorticaly and periventriculary was performed. Control scans 3, 6, 24 and 48 hours following myelography disclosed intracranial contrast media at level of basal cistern, the fourth ventricle and Sylvian fissure. Nine and eleven patients, respectively, had enhancement in the third and lateral ventricles. All patients had subcortical enhancement and nine patients had periventricular enhancement. At the first three hours after cervical myelography minor subcortical and periventricular edema was disclosed, which resolved during the subsequent hours. Two days after myelography, minimal residual contrast was disclosed subcortically at the level at the Sylvian fissure and in the subarachnoid space at the level of the Sylvian fissure and the convexity. It is recommended, that diagnostic cranial-CT is performed before cervical myelography or at a minimum of three days after cervical myelography.

Arachnoid cyst with complicating intracystic and subdural haemorrhage.

Intracranial arachnoid cysts are usually non-symptomatic. Intracystic and subdural haematomas induced by even minor head injury may turn an asymptomatic AC into a symptomatic one, necessitating surgical treatment. We present a case of a previous asymptomatic AC, spontaneously complicated with subdural hygroma and development of intracystic and subdural haematoma. Clinical follow-up and control CT regime of patients with AC are recommended.

Clinical and electrodiagnostic findings in breast cancer patients with radiation-induced brachial plexus neuropathy.

The clinical and neurophysiological characteristics of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients without signs of recurrent disease at least 60 months after radiotherapy (RT). Clinically, 35% (95% confidence limits: 25-47%) had RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-36%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%), assessment of a definite level was not possible. In most, symptoms began during or immediately after RT, thus being without significant latency. Numbness or paresthesias (71%, 52-86%) and pain (43%, 25-62%) were the most prominent symptoms, while the most prominent objective signs were decreased or absent muscle stretch reflexes (93%, 77-99%) closely followed by sensory loss (82%, 64-93%) and weakness (71%, 52-86%). Neurophysiological investigations were carried out in 46 patients (58%). The most frequent abnormalities in patients with RBP were signs of chronic partial denervation with increased mean duration of individual motor unit potentials, and decreased amplitude of compound muscle and sensory action potentials. Nerve conduction velocities were normal.

Radiation-induced brachial plexus neuropathy in breast cancer patients.

The incidence and latency period of radiation-induced brachial plexopathy (RBP) were assessed in 79 breast cancer patients by a neurological follow-up examination at least 60 months (range 67-130 months) after the primary treatment. All patients were treated primarily with simple mastectomy, axillary nodal sampling and radiotherapy (RT). Postoperatively, pre- and postmenopausal patients were randomly allocated chemotherapy or antiestrogen treatment. All patients were recurrence-free at time of examination. Clinically, 35% (25-47%) of the patients had RBP; 19% (11-29%) had definite RBP, i.e. were physically disabled, and 16% (9-26%) had probable RBP. Fifty percent (31-69%) had affection of the entire plexus, 18% (7-36%) of the upper trunk only, and 4% (1-18%) of the lower trunk. In 28% (14-48%) of cases assessment of a definite level was not possible. RBP was more common after radiotherapy and chemotherapy (42%) than after radiotherapy alone (26%) but the difference was not statistically significant (p = 0.10). The incidence of definite RBP was significantly higher in the younger age group (p = 0.02). This could be due to more extensive axillary surgery but also to the fact that chemotherapy was given to most premenopausal patients. In most patients with RBP the symptoms began during or immediately after radiotherapy, and were thus without significant latency. Chemotherapy might enhance the radiation-induced effect on nerve tissue, thus diminishing the latency period. Lymphedema was present in 22% (14-32%), especially in the older patients, and not associated with the development of RBP. In conclusion, the damaging effect of RT on peripheral nerve tissue was documented. Since no successful treatment is available, restricted use of RT to the brachial plexus is warranted, especially when administered concomitantly with cytotoxic therapy.

Intracranial iohexol-distribution following cervical myelography, postmyelographic registration of adverse effects, psychometric assessment and electroencephalographic recording.

Cervical myelography (CM) was taken from 14 cases with cervical root-compression symptoms. Prior to myelography, there was complete cranial CT registration to assess the subarachnoid, intraventricular, subcortical and periventricular densities. Control scans at 3,6,24 and 48 h following myelography disclosed intracranial contrast medium at level of basal cisterns, the fourth ventricle and fissura Sylvii. Nine and 11 patients, respectively, had enhancement in the third and lateral ventricles. All patients had subcortical enhancement, and 9 patients had periventricular enhancement; at the 3-h control CT after myelography a minor subcortical edema was disclosed, which declined during the following hours. Two days after myelography, a minimal residual contrast was disclosed subcortically at the level of fissura Sylvii and in the subarachnoid space at the level of fissura Sylvii and the convexity. Hence, we recommend, that diagnostic cranial CT is performed before or postponed until 3 days after cervical myelography. The patients were questioned about adverse effects, and they underwent psychometric assessment and EEG-recordings: 11 had adverse effects, chiefly mild and exclusively transient, without sequelae. Three patients had no side effect. The psychometric assessment, however, disclosed pronounced deterioration in all patients at test 28 h after myelography, especially marked in the verbal paired associates test, however these disturbances were totally absent at retest one week later. No EEG-abnormalities developed; consistently, no patient had seizures. In conclusion, following CM iohexol is taken up by the brain parenchyma, gradually disappearing within 48 h, during which time a brain CT will be disturbed. During the same period some deterioration of psychometric tests may be found.

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. MATERIAL & METHODS--Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. RESULTS--Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. CONCLUSION--The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.

Leber's hereditary optic neuropathy associated with a disorder indistinguishable from multiple sclerosis in a male harbouring the mitochondrial DNA 11778 mutation.

This report describes a multiple sclerosis (MS)-like disorder in a male patient with Leber's hereditary optic neuropathy (LHON) harbouring the mitochondrial DNA 11778 base pair mutation. Given the population frequencies of MS and LHON, coincidental occurrence is unlikely. Hypothetically the mitochondrial mutation underlying LHON may contribute to presumably immunologically mediated involvement of other myelinated axons in the central nervous system in susceptible individuals, producing a disorder indistinguishable from MS. We recommend that investigation for oligoclonal bands in CSF, evoked potentials and MR brain scan in these patients be supplemented with mitochondrial DNA analysis.

Prevention of thromboembolism in spinal cord injury: role of low molecular weight heparin.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major causes of morbidity and mortality in patients with acute spinal cord injury. Our preliminary studies indicated that low molecular weight heparin (LMWH) was significantly more effective than standard heparin in preventing these complications. We have now extended these studies by screening an additional 122 patients and treating 60 who met predefined criteria with LMWH in a dose of 3,500 anti-Xa U given subcutaneously once daily for 8 weeks. All patients were examined daily at bedside and had regularly scheduled venous ultrasonography; those with abnormalities had confirmatory venography and lung scans. Postmortem examinations were conducted in those who died. Forty completed the trial without incident, 6 had DVT (4 proximal and 2 distal), 1 had a fatal PE, 1 had postoperative bleeding requiring discontinuation of the LMWH, 10 were transferred or discharged, and 2 died of respiratory failure. The percentage of patients free of thrombosis or bleeding after 8 weeks of treatment was 85.9 +/- 5.0% standard error of mean (SEM). Thirty-three patients entered a follow-up observation period of 4 weeks without thromboprophylaxis; 2 weeks into this period 1 had a proximal DVT and 1 had a fatal PE; the course of the remainder was uneventful. We conclude that LMWH compares favorably with standard heparin in preventing venous thromboembolism, and is associated with significantly less bleeding. Eight weeks of prophylaxis seems adequate for most patients.