Intravitreal triamcinolone improves recovery of visual acuity in nonarteritic anterior ischemic optic neuropathy.

BACKGROUND: The visual outcome in untreated nonarteritic anterior ischemic optic neuropathy (NAION) is dismal. Because intravitreal triamcinolone (IVTA) has shown promise in improving edematous retinal disorders, a pilot trial of this therapy in NAION was considered reasonable. METHODS: Four eyes of 4 patients with severe visual loss due to NAION were treated with 4 mg IVTA (study group). The control group consisted of 6 consecutive patients with NAION who received no treatment. Patients were evaluated by the visual acuity and visual field measurements of the Early Treatment Diabetic Retinopathy Study (ETDRS) and fluorescein angiography. RESULTS: All patients completed at least 9 months of follow-up. In the study group, the mean improvement in visual acuity were 4, 5.8, and 6.2 ETDRS lines at the first and third weeks and final visit, respectively. Optic disc swelling and leakage had markedly decreased at the first postinjection week and had disappeared by the third week examination in all eyes. In the control group, the mean improvements in visual acuity were 0, 0.7, and 1.3 ETDRS lines at the first and third weeks and final visit, respectively. Control eyes showed resolution of the optic disc swelling between the fourth week and third month visits. No marked change in visual field defects was observed in either group. CONCLUSIONS: IVTA provided relatively improved recovery of visual acuity and relatively rapid resolution of optic disc swelling in a small sample of patients with acute NAION. It did not provide visual field improvement. A larger trial is merited by the results of this small pilot study.     

A severe case of neuroleukemiosis caused by B cell chronic lymphocytic leukemia,presenting as mononeuritis multiplex

Aims

To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex.

Methods

The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy.

Results

The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement.

Discussion

Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity.     

Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2

OBJECTIVE: Charcot-Marie-Tooth (CMT) neuropathy with visual impairment due to optic atrophy has been designated as hereditary motor and sensory neuropathy type VI (HMSN VI). Reports of affected families have indicated autosomal dominant and recessive forms, but the genetic cause of this disease has remained elusive. METHODS: Here, we describe six HMSN VI families with a subacute onset of optic atrophy and subsequent slow recovery of visual acuity in 60% of the patients. Detailed clinical and genetic studies were performed. RESULTS: In each pedigree, we identified a unique mutation in the gene mitofusin 2 (MFN2). In three families, the MFN2 mutation occurred de novo; in two families the mutation was subsequently transmitted from father to son indicating autosomal dominant inheritance. INTERPRETATION: MFN2 is a mitochondrial membrane protein that was recently reported to cause axonal CMT type 2A. It is intriguing that MFN2 shows functional overlap with optic atrophy 1 (OPA1), the protein underlying the most common form of autosomal dominant optic atrophy, and mitochondrial encoded oxidative phosphorylation components as seen in Leber's hereditary optic atrophy. We conclude that autosomal dominant HMSN VI is caused by mutations in MFN2, emphasizing the important role of mitochondrial function for both optic atrophies and peripheral neuropathies.     

Lasting reduction of severe spasticity after ending chronic treatment with intrathecal baclofen.

OBJECTIVE--To investigate whether the dose of intrathecal baclofen necessary for a sufficient reduction of muscle tone and spasms changes during treatment of severe spasticity. METHODS--A group of 27 patients received intrathecal baclofen for 61 (SD 18) months. RESULTS--Spasticity remained absent or strongly reduced after stopping the intrathecal baclofen infusion in seven patients. The dose of baclofen could be reduced to 40% of that dose which was originally necessary in 10 patients. The dose remained the same or increased slightly in 10 patients. Possible reasons for the continuing reduction of spasticity after terminating long term intrathecal baclofen infusion in some patients could be: lasting morphological changes in spinal cord neurons by second messenger controlled modulation of gene expression, a toxic effect of baclofen on spinal neurons, muscular atrophy, inflammation due to the catheter, or progression of multiple sclerosis. CONCLUSIONS--A higher initial daily dose of intrathecal baclofen might lead to a faster, lasting suppression of spasticity and the development of spastic symptoms might even be prevented by pre-emptive treatment with baclofen in patients with newly acquired lesions of the spinal cord.     

Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using 18F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.     

Electrophysiological assessment of visual function in patients with non-arteritic ischaemic optic neuropathy

Background and purpose:  Our study aims to evaluate retinal function and neural conduction in post-retinal visual pathways of patients with non-arteritic ischaemic optic neuropathy (NION).
Methods:  Twenty patients (mean age: 63.7 ± 5.96 year) with NION and 20 age-similar control subjects were enrolled. Simultaneous recording of pattern electroretinograms (PERGs) and visual evoked potentials (VEPs), and Log of minimum angle resolution (MAR) visual acuity (VA) were assessed in NION patients and controls.
Results:  Significantly ( anova , P  < 0.01) abnormal PERG and VEP responses, delayed retinocortical time (RCT, difference between VEP P100 and PERG P50 implicit times), and reduced VA were found in NION patients with respect to control subjects. The delay in RCT was not significantly (Pearson's test, P  > 0.01) correlated with the PERG impairment. The reduction in VA was significantly (Pearson's test, P  < 0.01) correlated to the increase in VEP P100 implicit time and RCT, whereas no correlations ( P  > 0.01) were found with PERG abnormalities.
Conclusions:  Non-arteritic ischaemic optic neuropathy patients with a reduction in VA may present two different, unrelated impairments: a dysfunction of the inner retinal layer (abnormal PERG) and abnormal post-retinal neural conduction (abnormal VEP and RCT). The reduction in VA seems to be related to the post-retinal impairment and seems to be independent from the retinal dysfunction.     

Occurrence of familial nonarteritic anterior ischemic optic neuropathy in a case series.

OBJECTIVE: To report on the occurrence of familial nonarteritic anterior ischemic optic neuropathy (NAION) in our NAION series. METHODS: One hundred forty-eight consecutive retrievable cases of NAION were surveyed regarding the occurrence of NAION in other family members. Medical records of affected family members were reviewed, and clinical characteristics of documented familial NAION cases were described. RESULTS: Of 79 patients who returned the survey, four reported one or more relatives with previously diagnosed NAION. There were nine cases of documented NAION in these four families. All cases occurred in siblings, with a mean age at onset of 55 years. Six patients had second eye involvement and in five, involvement became bilateral within 4 years after initial onset. None of the patients had diabetes; two had hypertension. CONCLUSION: A small number of patients with NAION may belong to a familial subclass. Three previous reports of familial NAION further support this hypothesis.     

Magnetic resonance imaging may simulate progressive multifocal leucoencephalopathy in a patient with chronic lymphocytic leukemia after fludarabine therapy

A 60-year-old male with chronic lymphatic leukemia (CLL) after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML). Cerebrospinal fluid Polymerase Chain Reaction (PCR) for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL).     

Glioblastoma multiforme following prophylactic cranial irradiation and intrathecal methotrexate in a child with acute lymphoblastic leukaemia : a case report.

A 12 year old boy with acute lymphoblastic leukaemia had received prophylactic cranial irradiation (2000 cGy/15 days) and intrathecal methotrexate. Six years later he was diagnosed to have glioblastoma in left temporoparietal region. There is a strong possibility that the glioma may have been radiation and/or chemotherapy induced.