Wolfram Syndrome. Case report.

Wolfram syndrome is a rare neurodegenerative and genetic disorder, characterized by insulin-dependent diabetes mellitus, caused by non-autoimmune loss of ß cells, as well as optic atrophy; the disease is also known as DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness). Patients that demonstrate diabetes mellitus are also affected by: optic atrophy in the first decade of their life, diabetes insipidus and sensorineural deafness in the second decade, and urinary tract and neurological abnormalities in the third decade of their life. Patients with Wolfram syndrome usually die due to central respiratory failures caused by brain stem atrophy in their third or at the beginning of their fourth decade of life. The authors present a case of two female siblings with diagnosed Wolfram syndrome that have been diagnosed with diabetes mellitus, optic atrophy, and urological abnormalities. Early diagnosis and adequate hormonal supplementation can improve their quality of life.

Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation.

Hereditary motor sensory neuropathy type VI (HMSN VI) is hereditary neuropathy accompanied by optic neuropathy. The feasibility of Coenzyme Q10 (CoQ10) as a treatment for subacute visual impairment of HMSN VI was examined. A 37-year-old patient with HMSN VI with a novel mitofusin 2 mutation was treated with high dose of CoQ10 (200 mg/day) for eight months. Visual impairment was partially resolved after CoQ10 therapy. High dose CoQ10 therapy may improve the prognosis of subacute visual impairment in HMSN VI. To confirm the effectiveness of CoQ10 on HMSN VI, further studies are needed.

[A case of Leber's neuroretinitis]. / A propos d'un cas de neurorétinite aiguë de Leber.

BACKGROUND: Described in 1916 by Theodore Leber, this rare syndrome characterized by low visual acuity, papillary edema, and a macular star (dry exsudates) occurs classically in the 30 to 40 year age range but also as frequently in children. The visual prognosis is excellent. An infectious cause is found in almost all cases. Case report A 34-year-old man consulted for declining visual acuity of the right eye which began suddenly without pain and was preceded by a flu-like syndrome lasting two weeks. Visual acuity on the right side was 2/10 P6, there was optic disk edema associated with dry macular exsudate (macular star) and a paleness of the posterior pole progressing to the periphery and readily visualized on the angiography, and a central scotome, but no dyschromatopsy. The left eye was strictly normal. Laboratory tests showed an erythrocyte sedimentation rate at 45, C reactive protein at 61, normal red cell count and minimal transaminase elevation. Spinal tap showed: 3 elements/mm(3), protein 0.28g/l, 18% gammaglobulins. Serology tests were negative. Brain imaging was normal. RESULTS: Corticosteroid flashes for three days were initiated and the patient was seen again two weeks later with clear clinical improvement. Visual acuity was 6/10 P2 with considerable resorption of the edema. DISCUSSION: This case is a typical illustration of acute Leber's neuroretinititis, probably caused by viral infection. The cerebrospinal fluid tests and brain imaging ruled out multiple sclerosis, and serology tests for syphilis, tuberculosis, Lyme disease and possible parasite infection were negative. CONCLUSION: Acute lever's neuroretinitis is an uncommon condition which must be distinguished from inflammatory optic neuropathy, particularly in multiple sclerosis which has a very different prognosis and clinical course.

Do idebenone and vitamin therapy shorten the time to achieve visual recovery in Leber hereditary optic neuropathy?

OBJECTIVES: The authors investigated the effectiveness of idebenone combined with vitamin B2 and vitamin C in the treatment of patients with Leber hereditary optic neuropathy (LHON) in an early stage as compared with untreated patients with LHON. These agents may stimulate the formation of ATP. MATERIALS AND METHODS: For this retrospective study, the authors selected 28 outpatients with LHON from the Keio University Hospital. These patients were followed for 2 to 19 years from disease onset. They were divided into two groups: 14 untreated patients (11778 mutation in 10 patients, 3460 mutation in 2 patients, and 14484 mutation in 2 two patients); and 14 treated patients (11778 mutation in 11 patients, 3460 mutation in 1 patient, and 14484 mutation in 2 patients). The treated patients were administered medical treatment with idebenone, vitamin B2, and vitamin C for at least 1 year. The current study evaluated the following: 1) number of eyes with visual recovery > or = 0.3; 2) interval between the onset of LHON and the beginning of visual recovery; 3) interval between the onset of LHON and visual recovery to 0.3; and 4) interval between the beginning of medical treatment and the beginning of visual recovery in the treated subjects. RESULTS: There was no significant difference in the number of eyes with visual recovery > or = 0.3 in the two groups with the 3460, 11778, or 14484 mutation. Patients with visual recovery showed a fenestrated scotoma or a clearing of central vision. The mean interval between the onset of LHON and the beginning of visual recovery was significantly shorter in the treated group (11.1 months) than in the untreated group (17.4 months) (P = 0.03). The mean interval between the onset of LHON and visual recovery to 0.3 was significantly shorter in the treated group (17.6 months) than in the untreated group (34.4 months) (P = 0.01). The mean interval between the initiation of medical treatment to the beginning of visual recovery was 5.4 months. CONCLUSIONS: Results suggest that the administration of idebenone, vitamin B2, and vitamin C sped the recovery of vision in patients with LHON.

Clinical and brain bioenergetics improvement with idebenone in a patient with Leber's hereditary optic neuropathy: a clinical and 31P-MRS study.

We used phosphorus magnetic resonance spectroscopy (31P-MRS) to study in vivo brain and muscle bioenergetics in a male patient with Leber's hereditary optic neuropathy (LHON) and mtDNA mutation at 11,778 bp who developed spastic paraparesis with white matter lesions on brain MR imaging. The study was performed before and during treatment with idebenone (135 mg t.i.d.) and after withdrawal. Clinical amelioration and worsening were associated with parallel changes in brain and skeletal muscle bioenergetics following the administration or withdrawal of idebenone. Reversal of paraparesis by idebenone was paralleled by normalization of 31P-MRS, serum lactate and central motor conduction. Extra-ocular neurological dysfunction in LHON may be amenable to treatment by appropriate quinones.

Clinical course of a cohort in the Cuban epidemic optic and peripheral neuropathy.

Nearly 51,000 Cubans were afflicted during an outbreak of an optic neuropathy (ON) and peripheral neuropathy (PN) between 1991 and 1993. We re-examined 14 of 20 affected individuals 16 months after an initial evaluation. The optic features were painless symmetric vision loss with poor visual acuity, color vision loss, central or cecocentral scotoma, optic disc pallor, and nerve fiber layer drop-out. The neurologic symptoms included stocking-glove sensory changes, hearing loss, leg cramps, sensory ataxia, hyperactive or absent reflexes, and complaints of memory loss. Two of 11 ON probands tested harbored Leber's hereditary optic neuropathy (LHON)-associated mitochondrial DNA mutations. All patients had received multivitamin therapy. We performed comparisons using the paired two-tailed t test. On re-examination, 12 of 14 patients demonstrated improvement. One patient remained unchanged. One woman with the nt-3460 mtDNA mutation showed a decline in vision. In patients not harboring mtDNA mutations, overall visual acuity, color vision, and peripheral neuropathy manifestations improved significantly (p < 0.001 for each manifestation). Most of the patients with Cuban ON and PN improved on multivitamin therapy. The significance of the mtDNA mutations is unclear. In the 2 LHON patients, manifestation of the disease may have been precipitated by nutritional deficiency. Patients with poor recovery or further deterioration should be evaluated for other factors, including poor vitamin therapy compliance and alternative diagnoses.

Lack of differences among mitochondrial DNA in family members with Leber's hereditary optic neuropathy and differing visual outcomes.

Investigation of a maternal family of three generations of Leber's hereditary optic neuropathy (LHON) showed four affected and three unaffected individuals. Two of the four patients had recovered near-normal vision, one spontaneously, and one following treatment with idebenone, a quinol compound. One patient whose visual impairment persisted was a heavy consumer of alcohol and tobacco. Molecular genetic analysis of 12 known primary or secondary mutations in mitochondrial DNA (mtDNA) associated with LHON revealed only the 11778 mutation in a homoplasmic fashion with no secondary mutations. The variations in clinical outcome thus could not be explained by synergistically interacting secondary mutations in mtDNA. Environmental factors may play an etiologic role in the development of optic atrophy.

Leber's hereditary optic atrophy: an atypical case with response to hydroxycobalamine therapy.

A 15-year old Chinese boy was diagnosed to have Leber's hereditary optic neuropathy (LHOA), having manifested with typical findings of bilateral severe visual loss and telangiectasia at the optic disc. However, no family history was elicited and an interval of more than 5 years separated visual loss in the two eyes. The latter is an extremely uncommon finding. Visual improvement was rapid and marked after instituting intramuscular hydroxycobalamine 5 mg weekly. Bilateral improvement of Snellen acuity to 6/9 was achieved within 6 months. This is also unusual in that visual prognosis is generally poor in LHOA, although spontaneous remissions have occasionally been recorded. In addition, the eye with a longer history of poor vision responded to therapy first.