Con Yiannikas

Axonal loss of retinal neurons in multiple sclerosis associated with optic radiation lesions

Objective: To investigate the potential links between thinning of retinal ganglion cell axons in eyes of patients with multiple sclerosis (MS) without past optic neuritis (ON) and MS-related inflammatory damage of the posterior visual pathway. Methods: Temporal retinal nerve fiber layer (tRNFL) thickness was analyzed in eyes with no history of ON (NON) from 53 patients with relapsing-remitting MS. Fifty normal age- and sex-matched controls were examined with optical coherence tomography. Low-contrast visual acuity charts were used for functional assessment of vision. The optic tract (OT) and optic radiation (OR) were identified using probabilistic tractography, and volume of T2 fluid-attenuated inversion recovery lesions and diffusion tensor imaging (DTI) indices were measured within both structures. Cross-sectional diameter of the OT was also calculated. Results: tRNFL thickness was significantly reduced in NON eyes and was associated with reduced low-contrast visual acuity. Lesions within the OR were detected in the majority of patients. There was a significant correlation between thinning of the tRNFL and OR lesion volume (adjusted for non-OR lesion volume, age, sex, and disease duration). tRNFL thickness also correlated with OR DTI indices. No OT lesions were identified in any of the patients and no relationship between retinal nerve fiber layer loss and potential markers of OT lesions was found. Conclusion: The results demonstrate a strong tract-specific association between loss of tRNFL fibers and MS-related inflammation within OR.

Treatment of proximal upper limb tremor with botulinum toxin therapy.

Proximal‐dominant upper limb tremor is highly disabling, and there is no effective medical therapy. In this study, we evaluated the efficacy of botulinum toxin (BTX) injections for the treatment of proximal tremor.

Treatment update in multiple sclerosis.

Multiple sclerosis is the most common cause of disability in young people in the Western world. Reduced life expectancy and worsening quality of life due to increasing disability later in the disease course have significant personal and societal costs. Changes in treatment strategies and newly available treatments hope to improve the outlook for our often young patients. This paper details currently available treatments and some that are expected to reach the market shortly.

Predicting a positive response to intravenous immunoglobulin in isolated lower motor neuron syndromes

Objective To determine clinically related characteristics in patients with pure lower motor neuron (LMN) syndromes, not fulfilling accepted diagnostic criteria, who were likely to respond to intravenous immunoglobulin (IVIg) treatment. Methods Demographic, clinical, laboratory and neurophysiological characteristics were prospectively collected from patients with undifferentiated isolated LMN syndromes who were then treated with IVIg. Patients were classified as either responders or non-responders to therapy with IVIg based on clinical data and the two groups were compared. Results From a total cohort of 42 patients (30 males, 12 females, aged 18-83 years), 31 patients responded to IVIg and 11 did not. Compared to patients that developed progressive neurological decline, responders were typically younger (45.8 compared to 56.0 years, P<0.05) and had upper limb (83.9% compared to 63.6%, NS), unilateral (80.6% compared to 45.5%, P<0.05), and isolated distal (54.1% compared to 9.1%, P<0.05) weakness. Patients with predominantly upper limb, asymmetrical, and distal weakness were more likely to respond to IVIg therapy. Of the patients who responded to treatment, only 12.9% had detectable GM1 antibodies and conduction block (not fulfilling diagnostic criteria) was only identified in 22.6%. Conclusions More than 70% of patients with pure LMN syndromes from the present series responded to treatment with IVIg therapy, despite a low prevalence of detectable GM1 antibodies and conduction block. Patients with isolated LMN presentations, not fulfilling accepted diagnostic criteria, may respond to IVIg therapy, irrespective of the presence of conduction block or GM1 antibodies, and should be given an empirical trial of IVIg to determine treatment responsiveness.

Significant dermatological side effects of intravenous immunoglobulin.

Intravenous immunoglobulin (IVIg) is an essential treatment for many neurological, immunological and haematological conditions. However, the severity of its rare adverse effects is often underrecognised. We report a series of 15 patients receiving IVIg for neurological and immunological disorders who developed severe skin reactions. Despite pre-medication, nearly all patients ceased IVIg due to the severity of the adverse response. Interestingly, the majority of patients were male and two-thirds were receiving treatment for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) or another inflammatory or demyelinating neuropathy. This marked propensity for male patients with CIDP to develop significant dermatological reactions following IVIg administration has not previously been described. Mechanisms involving the underlying autoimmunity inherent to this condition may play a role.

42.: Distal demyelinating neuropathy: Could it be neurolymphomatosis?

Lymphoma can affect virtually any organ system including the peripheral nervous system. Neuropathy associated with lymphoma may be secondary to direct invasion of lymphomatous cells (neurolymphomatosis), immune mechanisms, or as an adverse effect of chemotherapy or radiotherapy treatment. Establishing an accurate diagnosis is vital in order to initiate appropriate therapy, particularly in the case of neurolymphomatosis. Often determining the underlying pathological process is challenging as imaging and neurophysiological findings may be nonspecific. A 76-year-old man with diffuse large B-cell lymphoma presented with progressive asymmetrical muscle wasting, sensory loss and mild quadriparesis. Neurophysiology was consistent with a distal demyelinating sensorimotor neuropathy. Only minor enhancement of the right C8 nerve root was identified on MRI. In contrast, a whole body 18 F-fluorodeoxyglucose (FDG) positron emission tomography(PET)-CT scan showed avid linear FDG uptake in the brachial plexus bilaterally as well as multiple other sites, consistent with neurolymphomatosis. There was also evidence of active lymphoma in other organs including the liver and pleura. On subsequent scans the FDG PET-CT scan was the most reliable means to determine treatment response. The neurophysiological features of lymphomatous infiltration of the peripheral nervous system were recently described. Features of demyelination were frequently observed and a third of pathologically proven neurolymphomatosis cases fulfilled the European Federation of Neurological Societies/Peripheral Nerve Society electrodiagnostic criteria for definite chronic inflammatory demyelinating polyneuropathy. This case highlights the sensitivity of FDG PET-CT scan in establishing a diagnosis of neurolymphomatosis because MRI and cerebrospinal fluid analysis are often unhelpful or non-diagnostic. This case also emphasises that neurolymphomatosis should be considered in demyelinating neuropathies associated with lymphoma even when there are minimal or no MRI changes.

7.: Antibodies targeting myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

Autoantibodies such as those targeting aquaporin-4 are important biomarkers in central nervous system demyelination. We examined a cohort of patients with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder (NMOSD) for serum antibodies against the autoantigen myelin oligodendrocyte glycoprotein (MOG). We performed a flow cytometry cell-based assay using live human embryonic kidney 293 cells lentivirus-transduced to express full-length surface MOG. We tested the serum of 23 adult patients with aquaporin-4 antibody seronegative NMOSD, including bilateral and recurrent optic neuritis (BON; nxa0=xa011), longitudinally extensive transverse myelitis (LETM; nxa0=xa010), and sequential BON and LETM (nxa0=xa02), as well as patients with multiple sclerosis (MS; nxa0=xa076), and controls (nxa0=xa052), for the presence of MOG antibodies (MOG-Abs). MOG-Abs were detected in 9/23 patients with aquaporin-4 antibody seronegative NMOSD compared to 1/76 MS patients and 0/52 controls (p

Clinical and neurophysiological predictors of response to intravenous immunoglobulin in lower motor neuronopathies

Objective: To determine the clinical and neurophysiological factors on presentation that predict a response to intravenous immunoglobulin (IVIG) in patients presenting with lower motor neuronopathy. Methods: Medical records of 28 patients treated with IVIG for lower motor neuronopathy were studied. Baseline clinical, neurophysiological and laboratory parameters were compared between responders and non-responders to IVIG. Results: There were 15 responders and 13 non-responders. Responders were younger (41.73 vs 52.46 years) and more likely to have antiganglioside antibodies (46.15% vs 0%). Fasciculations were identified in responders and non-responders, but were confined to clinically affected muscles in responders. 53.33% of responders and 15.38% of non-responders met criteria for conduction block. Spontaneous discharges and fibrillations on electromyography were less common in responders than nonresponders, though fasciculations were equally present in both groups. Electromyographic discharges were only seen in responders in conjunction with conduction block. Conclusion: No single clinical, laboratory or conventional neurophysiological characteristic accurately predicts response to IVIG in all patients. Further study and application of new techniques are required. Younger patients who present with a lower motor neuronopathy without widespread fasciculations or spontaneous discharges on electromyography may respond to treatment with IVIG, whether or not conduction block and anti-GM1 antibodies are demonstrated.