Juvenile myasthenia gravis associated with autoimmune channelopathy and mixed connective tissue disease

Background/Aims: Ion channels are crucial elements in neuronal signaling and synaptic transmission. Autoantibodies against voltage-gated ion channels cause disorders in neuromuscular transmission. Autoantibodies against voltage-gated potassium channels (VGKC-Abs) are associated with acquired neuromyotonia and related disorders such as Morvan's syndrome and limbic encephalitis. The symptoms of myasthenia gravis reflect dysfunction of neuromuscular transmission. Methods and results: We present a 15-year-old girl with ptosis, proximal muscle weakness, neuromyotonia, hyperhidrosis, short memory loss and confusion. AntinAChR antibodies were positive. Electromyography showed neuromyotonic discharges. Cerebrospinal fluid analysis revealed oligoclonal bands. The plasma VGKC-antibody titer was elevated (176 pM, controls 100 pM), along with positive antiganglioside antibodies (GM1, asialo GM1, GM2, GD1a,b) and SS-A 211 U/mL, SS-B 157 U/mL, U1-RNP 188 U/mL, DNA-topo 128 U/mL (control <100). Brain magnetic resonance imaging was normal. The girl was treated with pyridostigmine, steroids, intravenous immunoglobulins and azathioprine, and repetitive plasma exchanges. Neurological impairments and myasthenic crisis occurred in periods of 5-21 days. Conclusion: The neuromyotonia and some of the dysautonomic features are likely to be directly related to the VGKC antibodies in the peripheral nervous system. The central nervous system symptoms are very likely to be due to the direct effects of VGKC antibodies, although there can be some other autoantibodies. A severe clinical course might be related to myasthenia gravis associated with autoimmune disease of the central and peripheral nervous system overlapping probably with mixed connective tissue disease

Characteristics and outcomes of children with primary oxalosis requiring renal replacement therapy.

Item does not contain fulltextBACKGROUND AND OBJECTIVES: Primary hyperoxaluria (PH) as a cause of ESRD in children is believed to have poor outcomes. Data on management and outcomes of these children remain scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study included patients aged <19 years who started renal replacement therapy (RRT) between 1979 and 2009 from 31 countries providing data to a large European registry. RESULTS: Of 9247 incident patients receiving RRT, 100 patients had PH. PH children were significantly younger than non-PH children at the start of RRT. The median age at RRT of PH children decreased from 9.8 years in 1979-1989 to 1.5 years in 2000-2009. Survival was 86%, 79%, and 76% among PH patients at 1, 3, and 5 years after the start of RRT, compared with 97%, 94%, and 92% in non-PH patients, resulting in a three-fold increased risk of death over non-PH patients. PH and non-PH patient survival improved over time. Sixty-eight PH children received a first kidney (n=13) or liver-kidney transplantation (n=55). Although the comparison was hampered by the lower number of kidney transplantations primarily derived from the earlier era of RRT, kidney graft survival in PH patients was 82%, 79%, and 76% at 1, 3, and 5 years for liver-kidney transplantation and 46%, 28%, and 14% at 1, 3, and 5 years for kidney transplantation alone, compared with 95%, 90%, and 85% in non-PH patients. CONCLUSIONS: The outcomes of PH children with ESRD are still poorer than in non-PH children but have substantially improved over time.1 maart 201