Nasu-Hakola disease (NHD-polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy; PLOSL) is a rare autosomal recessive disorder, caused by mutations in two genes: TREM 2 and DAP 12. NHD is characterized by a combination of diffuse bone cysts and pre-senile dementia.Most of the NHD cases first present in early adulthood with skeletal abnormalities (osseous phase).Neurological symptoms manifest in the fourth decade of life as prefrontal syndrome 1,2,3 .A 32 year-old male patient presented bone fractures, usually after minor traumas and cystic lesions on X-Rays (Figure 1).He denied any personality change or memory disturbances.The neurological examination was normal.The neuropsychological tests displayed only easy distractibility.CT and MRI demonstrate abnormalities in the basal ganglia and white matter (Figure 2) showing that imaging findings precedes neuropsychiatric symptoms.

Objective: Vanishing white matter (VWM) is an autosomal recessive leukoencephalopathy characterized by slowly progressive ataxia and spasticity with additional stress-provoked episodes of rapid and major deterioration. The disease is caused by mutations in the genes encoding the subunits of eukaryotic initiation factor 2B, which is pivotal in translation of mRNAs into proteins. The disease onset, clinical severity, and disease course of VWM vary greatly. The influence of genotype and gender on the phenotype is unclear. Methods: From our database of 184 patients with VWM, we selected those with the following mutations in the gene EIF2B5: p.Arg113His in the homozygous state (n = 23), p.Arg113His in the compound-heterozygous state (n = 49), p.Thr91Ala in the homozygous state (n = 8), p.Arg113His/p.Arg339any (n = 9), and p.Thr91Ala/p.Arg339any (n = 7). We performed a cross-sectional observational study. Evaluated clinical characteristics were gender, age at onset, age at loss of walking without support, and age at death. Means, male/female ratios, and Kaplan-Meier curves were compared. Results: Patients homozygous for p.Arg113His had a milder disease than patients compound heterozygous for p.Arg113His and patients homozygous for p.Thr91Ala. Patients with p.Arg113His/p.Arg339any had a milder phenotype than patients with p.Thr91Ala/p.Arg339any. Overall, females tended to have a milder disease than males. Conclusions: The clinical phenotype in VWM is influenced by the combination of both mutations. Females tend to do better than males.

Inflammatory orbital complications of strabismus surgery are a rare occurrence. They include cellulitis, subconjunctival and sub-Tenon's abscesses, myositis, and endophthalmitis. The incidence of periocular infection is assumed to be one case per 1,100 surgeries. In this report, we describe a case of sub-Tenon's abscess after strabismus surgery.

Magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) data were obtained in a patient with giant axonal neuropathy (GAN) and compared to a control group. Fractional anisotropy (FA) and apparent coefficient diffusion (ADC) data were obtained from specific white matter tracts including the corticospinal tracts (CST), corpus callosum (CC), optic radiations (OR), and middle cerebellar peduncle (MCP). Analysis of the MRS was performed. DTI parameters and MRS results were correlated with the neuropathological findings described for GAN. No significant difference between the FA of the CC of the patient and the control group was found. However, there was a significant difference between the FA of the CST, OR, and MCP of the patient and the control group. The ADC values for all tracts of the patient were significantly increased. N-acetylaspartate to creatine (NAA/Cr) and N-acetylaspartate to choline (NAA-Cho) (choline) metabolite ratios were slightly decreased and choline to creatine (Cho/Cr) and myo-inositol to creatine (Ins/Cr) metabolite ratios were increased in the parietal gray and white matter of the patient as compared to the control group. Cerebellar involvement was less evident. The DTI and MRS findings suggest myelin and axonal damage.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive cerebral white matter disorder in children. This disease. is histopathologically characterized by myelin splitting and intramyelinic vacuole formation. MLC is caused by mutations in the gene MLC1, which encodes a novel protein, MLCL Since the first report, 50 mutations in this gene have been found. Mutations occur throughout the entire coding region and include all different types: 11 splice-site mutations; one nonsense mutation; 24 missense mutations; and 14 deletions and insertions. Until now, six polymorphisms within the coding sequence of MLC1 had been reported. In about 20% of the patients with a typical clinical and MRI picture, no mutations in the MLC1 gene are found. Several of the families, in which no mutations are found, also do not show linkage with the MLC1 locus, which suggests a second gene involved in MLC. The absence of mutations may also be the consequence of performing standard mutation analysis that can miss heterozygous deletions, mutations in the promoter, 3' and 5' untranslated regions (UTRs), and intron mutations, which may influence the amino acid composition of the end product. In this work we describe 13 novel mutations, including those found with extended mutation analysis on MLC patients. This study shows that extended mutation analysis is a valuable tool to identify at least some of the missing mutations. Therefore, we suggest extended mutation analysis for the MLC1 gene, if no mutations are found during standard analysis.

Vanishing white matter is a leukoencephalopathy that usually affects young children. Five genes were found recently for this disease, allowing a DNA-based diagnosis. The authors describe six patients homozygous for the Arg113His mutation in eIF2Bepsilon. Only one had a childhood onset; four had a later onset and a protracted disease course; one adult still has no symptoms. Our data suggest that the Arg113His mutation is particularly mild and should be considered in the differential diagnosis of adult diffuse leukoencephalopathies, independent of whether there are associated clinical signs, an episodic course, or MRI shows white matter rarefaction/cystic degeneration.

Devic's neuromyelitis optica is a clinical entity characterized by severe transverse myelitis, acute unilateral or bilateral optic neuropathy, no clinical involvement beyond the spinal cord or optic nerves and a monophasic or recurrent evolution. We report two cases, both female, affected by spinal cord and visual symptoms suggesting Devic's neuromyelitis. First patient, a 30 y.o. woman, was admitted due to acute flaccid tetraparesis preceded by left optic neuropathy five months before. CSF showed normal IgG level and no synthesis of oligoclonal bands. Brain and spinal cord MRI showed left optic neuropathy, signal hyperintensities at cervical and thoracic levels on the T2 weighted sequence, and diffuse enhancement after e.v. gadolinium DPTA. Second patient presented optical neuropathy at 19 years of age, transverse myelitis at 47 years of age, and a new cervical myelopathy two years later, at 49 y.o. Brain and spinal cord MRI showed bilateral optic atrophy and multiple hyperintensities among C1/C2 and C6/C7 levels, some of them cavitated. Pleocytosis, protein count of 511 mg/dl, presence of IgGs but negative oligoclonal bands was observed on CSF. In general, Devic's optic neuromyelitis has poor functional prognoses, recurrences may follow onset affecting spinal cord and optic nerves. In our two cases, we did not identify a specific cause despite all the diagnostic work-up.

Introduction. Tropical spastic paraparesis due to HTLV-I virus is diagnosed at very advanced stages, when there is spinal atrophy present and so only symptomatic treatment can be given. Early diagnosis of HTLV-I infection in unusual syndromes and the use of corticosteroids may help to slow the development of the disease. Clinical cases. We describe two Brazilian patients who developed symptoms due to HTLV-I present for less than one year: subacute myelopathy with a sensory level and an ataxic pyramidal syndrome associated with aronal neuropathy, which partly improved after treatment with corticosteroids. Results. A 50 year old woman presented with progressive paraparesis following pain, cramps, feeling that her legs had 'gone to sleep' and sphincter dysfunction over the previous eleven months. Spinal MR showed a diffuse spinal hypersignal at DZ. The 60 year old man had developed an ataxic syndrome and axonal polyneuropathy over the previous ten months. In both patients the anti-HTLV antibodies in blood and CSF were positive on ELISA as Infer confirmed by Western-blot. Thorough biochemical study ruled out of her infectious etiologies. Both patients were treated with corticosteroids (IV methyl-prednisolone and oral prednisone respectively) and their symptoms improved particularly the joint pains, ataxia and the 'gone to sleep' sensation of the legs. Conclusions. The ataxic syndrome and myelopathy due to HTLV-I, when these have been diagnosed early, may benefit from corticosteroid treatment and progression of the disorder be prevented The myelitic phase of HTLV-I infection is associated with diffuse myelopathy, which was unusally seen in our first patient on spinal MR.