Standardized Tapering off Subcutaneous Immunoglobulin in Chronic Inflammatory Demyelinating Polyneuropathy.

BACKGROUND: Attempting discontinuation of treatment in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) is recommended. However, there is no evidence based regimen for tapering off subcutaneous immunoglobulin (SCIG). This trial investigated stepwise tapering off SCIG to detect remission and the lowest effective dosage. During tapering off, frequent vs less frequent clinical evaluation was compared. METHODS: Patients with CIDP receiving a stable SCIG dosage followed a standardized tapering off regimen: 90%, 75%, 50%, 25% and 0% of the initial dose every 12th week, pending no deterioration occurred. In case of relapse during tapering off, the lowest effective dose was identified. Treatment with SCIG was registered for two years after participation. Disability score and grip strength were primary parameters. Participants were randomized to clinical evaluation every 6th week (frequent) or 12th week (less frequent). RESULTS: Fifty-five patients were included of which thirty-five relapsed. Twenty patients (36%) were able to discontinue treatment without relapse. In relapsing patients, median dosage could be reduced by 10% (range, 0-75). After two years, 18 of 20 patients were still in remission without treatment. Frequent clinical evaluation did not detect deterioration more frequently than less frequent evaluation; RR 0.5 (95% CI, 0.2-1.2) (p = 0.17). CONCLUSION: In stable CIDP patients, SCIG could be completely tapered off in 36% of the patients and only in 10% of these patients relapse occurred during the following two years. More frequent evaluation was not superior to detect deterioration.

[Chronic inflammatory demyelinating polyneuropathy].

In this review, we discuss chronic inflammatory demyelinating polyneuropathy (CIDP), which is a disease with proximal and distal weakness and sensory disturbances resulting in impaired daily activity. The diagnosis is based on the clinical presentation and electrophysiology demonstrating demyelination in the peripheral nerves. CIDP can be successfully treated with immunoglobulin, glucocorticoids or plasma exchange, and during the latest decade, immunoglobulin has been administered subcutaneously improving patients' flexibility and autonomy. By time, 30% of the patients will remit, and maintenance treatment will no longer be necessary.

[Fatal cachexia caused by mitochondrial neuro-gastro-intestinal encephalomyopathy].

In this case report, a 23-year-old normal-functioning young man was repeatedly admitted to the hospital with mal-nutrition and pseudo-obstruction. External ophthalmoplegia, global muscular atrophy and demyelinating sensory-motor-autonomic neuropathy became evident. An MRI showed symmetrical white matter lesions and muscle biopsy atrophic muscle fibres. A TYMP mutation confirmed the diagnosis, and the patient had a rapidly fatal disease course. Mitochondrial neuro-gastro-intestinal encephalo-myopathy is rare and often overlooked. In less advanced disease, stem cell transplantation can correct thymidine phosphorylase deficiency.

Retrospective correlation analysis of plasma Immunoglobulin G and clinical performance in CIDP.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) can be successfully treated with immunoglobulin either intravenously (IVIG) or subcutaneously (SCIG). Measurement of plasma immunoglobulin G levels (P-IgG) and its correlation to clinical improvement has shown conflicting results. This study aims to clarify whether changes in P-IgG are related to clinical development in patients with CIDP treated with IVIG or SCIG. METHODS: Patients from five previous studies treated with either IVIG or SCIG with evaluation at baseline and re-evaluation after two or 10/12 weeks, respectively were included. At evaluation and re-evaluation, the following tests were done: combined isokinetic muscle strength (cIKS), grip strength, 9-hole-peg test (9-HPT), 40-meter-walk test (40-MWT), clinical examination of muscle strength score by the Medical Research Council (MRC) and measurement of plasma immunoglobulin G (P-IgG). RESULTS: Fifty-five patients were included in the IVIG group and 41 in the SCIG group. There was no correlation between the changes in P-IgG and cIKS in neither the IVIG group (r = 0.137, p = 0.32) nor the SCIG group (r =  - 0.048, p = 0.77). Similarly, no correlations could be demonstrated between P-IgG and grip strength, 9-HPT, 40-MWT or MRC. CONCLUSIONS: In patients with CIDP receiving SCIG or IVIG, changes in P-IgG during treatment did not correlate with changes in muscle strength or other motor performance skills.

[Autonomic autoimmune ganglionopathy in a patient with newly diagnosed Type 1 diabetes].

In this case report, a 50-year-old previously healthy woman presented with autonomic autoimmune ganglionopathy (AAG) as well as possible treatment-induced neuropathy of diabetes only one month in the aftermath of acute onset of Type 1 diabetes. AAG is an acquired neurological syndrome, presenting itself with diffuse, mostly acutely developing autonomic failure. This case illustrates the debut of two possibly autonomic diseases in very close temporal relation, and thus shows the complexity of autoimmune disease.

Does grip strength reflect isokinetic muscle strength in lower limbs in patients with chronic inflammatory demyelinating polyneuropathy?

INTRODUCTION: Grip strength (GS) is a common measure of general muscle strength in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). However, it is important to investigate the correlation and responsiveness of GS compared with isokinetic muscle strength (IKS) and function of the lower limbs. METHODS: Seventy patients with CIDP were evaluated with GS, IKS, and functional measures of the lower limbs. Reevaluation was performed after 2 and 10/12 weeks. Correlation and response analyses were performed. RESULTS: GS correlated with IKS at the ankle (IKSankle ; maximum Spearman's rank-order correlation [RS ] = 0.58) and with walking performance (maximum RS = -0.38). IKSankle was more responsive to detect change (standardized response mean [SRM] = 0.57) than GS (SRM = 0.27). DISCUSSION: GS does not seem to be an appropriate surrogate measure of IKS and function of the lower limbs in patients with CIDP. Muscle Nerve 58: 449-452, 2018.

Resistance training and aerobic training improve muscle strength and aerobic capacity in chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: We investigated the effects of aerobic and resistance exercise in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Eighteen CIDP patients treated with subcutaneous immunoglobulin performed 12 weeks of aerobic exercise and 12 weeks of resistance exercise after a run-in period of 12 weeks without exercise. Three times weekly the participants performed aerobic exercise on an ergometer bike or resistance exercise with unilateral training of knee and elbow flexion/extension. Primary outcomes were maximal oxygen consumption velocity (VO2 -max) and maximal combined isokinetic muscle strength (cIKS) of knee and elbow flexion/extension. RESULTS: VO2 -max and muscle strength were unchanged during run-in (-4.9% ± 10.3%, P = 0.80 and -3.7% ± 10.1%, P = 0.17, respectively). Aerobic exercise increased VO2 -max by 11.0% ± 14.7% (P = 0.02). Resistance exercise resulted in an increase of 13.8% ± 16.0% (P = 0.0004) in cIKS. DISCUSSION: Aerobic exercise training and resistance exercise training improve fitness and strength in CIDP patients. Muscle Nerve 57: 70-76, 2018.

Comparisons in fluctuation of muscle strength and function in patients with immune-mediated neuropathy treated with intravenous versus subcutaneous immunoglobulin.

INTRODUCTION: Variations in muscle strength and function have not been studied in patients with chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy whose treatment regimen has been changed from intravenous to subcutaneous immunoglobulin (IVIg to SCIg). METHODS: In a prospective, open-label study, patients were changed from monthly IVIg to weekly SCIg. The primary endpoint was variation in isokinetic muscle strength (cIKS). Secondary endpoints were variations in Medical Research Council (MRC) score, grip strength (GS), 9-hole-peg test (9-HPT), and 40-meter-walk test (40-MWT). RESULTS: The coefficient of variance of cIKS during the IVIg and SCIg treatment periods was unchanged (mean ± SD: 6.97 ± 4.83% vs. 5.50 ± 3.13%, P = 0.21). The variations in the 9-HPT and 40-MWT were significantly lower in the SCIg group (P = 0.01 and P = 0.005, respectively). DISCUSSION: When therapy was changed from IVIg to SCIg, fluctuation of muscle strength was unchanged, but performance fluctuations were diminished. Muscle Nerve 57: 610-614, 2018.

Improvement of hemoglobin levels after a switch from intravenous to subcutaneous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

BACKGROUND: Intravenous immunoglobulin (IVIG) is recommended treatment for chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Recent studies have demonstrated that subcutaneous immunoglobulin (SCIG) is feasible, safe, and effective in both disorders. IVIG leads to transient hemolysis and, consequently, we hypothesized that frequent small doses of SCIG exerts less hemolytic activity than a few larger doses of IVIG. STUDY DESIGN AND METHODS: In an open-label study, 23 three patients treated with IVIG for CIDP or MMN were switched to SCIG at an equal dosage. IVIG was administered two to three times for 6 weeks. Two weeks after the last IVIG infusion at Week 8, SCIG was initiated with injections twice or thrice weekly until Week 20. Blood samples were drawn 2 weeks after IVIG at Weeks 2 and 8 and during SCIG at Weeks 14 and 20 determining hemoglobin (Hb) and hemolytic variables. RESULTS: Seventeen patients completed the study. At enrollment, the Hb level was 138 ± 12 g/L, haptoglobin level was 1.4 ± 0.5 g/L, reticulocyte count was 58.7 × 109  ± 21.3 × 109 /L, and bilirubin level was 6.6 ± 2.3 µmol/L. The average of the two blood samples drawn at comparable intervals during IVIG and SCIG showed that Hb increased from 135 ± 15 to 138 ± 15 g/L (p = 0.03). During IVIG the hemolytic variables showed signs of mild hemolysis that improved during SCIG, haptoglobin increasing from 1.2 ± 0.5 to 1.5 ± 0.6 g/L (p = 0.002), reticulocytes decreasing from 71.9 × 109  ± 35.8 × 109 to 54.5 × 109  ± 16.3 × 109 /L (p = 0.02), and bilirubin decreasing from 7.3 ± 2.8 to 5.8 ± 1.8 µmol/L (p = 0.001). CONCLUSION: A switch from IVIG to SCIG was associated with a slight increase of Hb levels and an improvement of laboratory variables related to hemolytic activity.

Headache and Nausea after Treatment with High-Dose Subcutaneous versus Intravenous Immunoglobulin.

Treatment with intravenous immunoglobulin (IVIG) leads to transient side effects such as headache and nausea during and after the infusion. We hypothesized that subcutaneous administration of smaller doses of immunoglobulin (SCIG) given more frequently leads to less severe headache and nausea and could be an alternative in patients experiencing side effects. Fifty-nine patients diagnosed with neurological disorders (chronic inflammatory demyelinating polyneuropathy (CIDP), multi-focal motor neuropathy (MMN) or post-polio syndrome) were treated with IVIG, and 27 CIDP or MMN patients with SCIG. For two consecutive weeks daily, registration of the severity of headache and nausea was registered on a visual analogue scale (VAS) from 0 to 100 mm. In the SCIG group, headache reached a peak value of 1 (0-13) mm at day 6 versus 11 (0-96) mm in the IVIG group at day 4 (p < 0.0001). For nausea, the SCIG group had a stable value of 0 (0-21) mm at all days, whereas a peak value of 3 (0-90) mm was reached at day 4 in the IVIG group (p < 0.0001). SCIG leads to less severe headache and nausea than IVIG without fluctuations of side effects in relation to the injections.

[Spontaneous cerebrospinal fluid leak may cause intracranial hypotension]. / Spontan cerebrospinalvæskelækage kan give intrakraniel hypotension.

Spontaneous intracranial hypotension (SIH) is often misinterpreted as migraine or tension headache. This type of headache is, however, orthostatic and resolves in supine position. CT scan/MRI of the brain has characteristic findings, enhancement of the pachymeninges and bilateral hygroma. An extreme situation of a 70-year-old woman with sagging midbrain is described in this case report. Although this type of headache may be caused by a dural fistula with spinal fluid leak it is not necessary to locate the lesion with myelografi/MR. Timely treatment with an epidural blood patch at any lumbal level could prevent potentially life-threatening complications and the headache resolved within hours/few days.

Myopathic EMG findings and type II muscle fiber atrophy in patients with Lambert-Eaton myasthenic syndrome.

OBJECTIVE: Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. A few reports have described that EMG in LEMS may show changes compatible with myopathy, and muscle biopsies have been described with type II as well as type I atrophy. The EMG results were, however, based on qualitative EMG examination and the histopathological methods were not always clear. The objective of this study was to investigate if the previous EMG findings could be confirmed with quantitative EMG (QEMG) and to describe muscle histology in LEMS. METHODS: QEMG, nerve conduction studies and muscle biopsy were performed in four consecutive LEMS patients. RESULTS: QEMG showed significantly decreased mean MUP duration and muscle biopsy showed marked type II fiber atrophy. CONCLUSION: EMG and biopsy abnormalities mimicking myopathy may often be found in patients with LEMS. SIGNIFICANCE: LEMS is a debilitating, but treatable disease, which often precedes detection of a malignancy and it is therefore of obvious importance to diagnose these patients with speed and certainty. Hence it is important that neurophysiologists and neurologists are aware that EMG and histological abnormalities mimicking myopathy may be found in LEMS patients so that these findings do not prolong or misdirect the diagnostic process in these patients.

[Anti-thyroid antibodies in two patients with subacute dementia, ataxia, and myoclonus]. / Antithyroideaantistof hos to patienter med subakut dementiel udvikling, ataksi og myoklonus.

Hashimoto encephalitis (HE) is a steroid-responsive autoimmune encephalitis with anti-thyroid antibodies; Creutzfeldt-Jakob disease (CJD) is a prion disease. Both disorders can have a similar clinical presentation. Two women, 67 and 63 year-old, with subacute dementia, ataxia, myoclonus and positive antithyroid antibodies were given oral steroids. Whereas one progressively declined and had histopathologically proven CJD, the other made a complete recovery and was diagnosed with HE. Anti-thyroid antibodies can occur in CJD, but when present in a patient with subacute dementia, ataxia and myoclonus, a steroid trial always seems indicated.

Nitric oxide-induced headache may arise from extracerebral arteries as judged from tolerance to isosorbide-5-mononitrate.

Long-term exposure to organic nitrates influences different sections of the vascular bed heterogeneously. Continuous dosage of nitrates leads to the development of tolerance both to the vascular effects and to the unwanted adverse effect, headache. Human data on the development of tolerance in different cranial arteries over more than 24 h are lacking. We compared the vascular changes of the middle cerebral, superficial temporal and radial arteries during oral administration of isosorbide-5-mononitrate (5-ISMN) 30 mg three times daily for 7 days in 11 healthy subjects in a double-blind, randomised, placebo controlled cross-over design. Blood velocity in the middle cerebral artery was measured with transcranial Doppler and the diameters of the temporal and radial arteries were measured with high frequency ultrasound. Headache recordings were compared to the observed vascular changes over time. Tolerance was complete within 24 h in the middle cerebral artery whilst in the superficial temporal and the radial arteries, tolerance was only partial and developed much more slowly, i.e. after 7 days correlating with the disappearance of NO-induced headache. The present study thus demonstrated the important differences in the time profiles of appearance of nitrate tolerance in arteries of different vascular beds in man. If vasodilatation is the cause of NO-induced headache the results point to extracerebral arteries as the locus of nociception. Due to a variety of other possible pain-inducing effects of nitric oxide our results do not exclude cerebral arteries.

[Pandysautonomia. Severe autonomic dysfunction accompanying polyneuropathy]. / Pandysautonomi. Svoer autonom dysfunktion ledsagende polyneuropati.

The case of a young woman with complete autonomic paralysis following an event of respiratory and gastrointestinal infections is described. The diagnosis was based upon clinical, neurophysiological, and laboratory findings. In view of the occurrence of identical--although less pronounced--autonomic disturbances in some cases of Guillain-Barré syndrome and the high incidence of minor degrees of weakness, paresthesias, reflex loss, and CSF protein elevation in dysautonomic polyneuropathy, it seems likely that the latter disorder is also an immune polyneuropathy affecting the autonomic fibers within the peripheral nerves.