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Biomedical subjects

N R Miller

Publications and source records attributed to N R Miller.

At least 109 records · Page 6Linked to original sources
PubMed1993

Leber's hereditary optic neuropathy. Clinical manifestations of the 14484 mutation.

OBJECTIVE: To define the clinical features of Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation and to compare these features with those associated with three other pathogenetic mutations. DESIGN AND PATIENTS: Clinical and historical data were collected from 19 visually symptomatic patients from 17 independent pedigrees with the molecularly confirmed 14484 mutation. MAIN OUTCOME MEASURES: Demographic features, age of onset of visual loss, nadir of visual acuity, occurrence and timing of visual recovery, family history of visual loss, and associated medical and environmental conditions. RESULTS: Clinical characteristics associated with the 14484 mutation are similar overall to those of the three other primary mutations. One notable distinguishing feature is the higher incidence of visual recovery among patients with the 14484 mutation. Thirty-seven percent of our patients experienced visual recovery compared with 5% with the 11778 mutation (P < .001), 22% with the 3460 mutation, and 29% with the 15257 mutation. The average age of onset of visual symptoms for the patients with the 14484 mutation who had visual recovery was younger than for those without recovery (19.6 vs 30.6 years). Thirteen of the 19 patients had a history of metabolic disturbance, trauma, or substance abuse. CONCLUSIONS: Leber's hereditary optic neuropathy associated with the 14484 mitochondrial DNA mutation may have a better prognosis for visual recovery. The phenotypic expression of the 14484 mutation may be influenced by concurrent medical and environmental factors. Molecular genetic testing in suspected Leber's hereditary optic neuropathy is useful to confirm the diagnosis and to assess visual prognosis.

Adolescent↗
PubMed1993

Leber's hereditary optic neuropathy masquerading as tobacco-alcohol amblyopia.

OBJECTIVE: To determine the frequency of known primary mitochondrial DNA (mtDNA) mutations for Leber's hereditary optic neuropathy (LHON) in patients previously diagnosed as having tobacco-alcohol amblyopia. DESIGN: A case series of 12 patients with tobacco-alcohol amblyopia. Follow-up ranged from 2 months to 15 years. SETTING: Tertiary care. PATIENTS: Twelve patients diagnosed as having tobacco-alcohol amblyopia, based on the classic clinical presentation, were tested for all the known primary mtDNA mutations associated with LHON. All patients had a history of heavy alcohol or tobacco use or both. Twelve other patients who fit inclusion criteria were unable to be contacted or refused to participate in the study. MAIN OUTCOME MEASURES: Presence of a known primary mutation for LHON at nucleotide positions 11778, 3460, 15257, or 14484 of mtDNA. RESULTS: Two (17%) of 12 patients previously diagnosed as having tobacco-alcohol amblyopia tested positive for known LHON genetic mutations, one for the 11778 mutation and one for the 3460 mutation. CONCLUSIONS: The diagnosis of LHON should be considered in all patients diagnosed as having tobacco-alcohol amblyopia, particularly those with visual acuities of 20/200 or less. The availability of molecular genetic testing for LHON now allows confirmation of the diagnosis of LHON in patients who otherwise may be misdiagnosed.

Adult↗
PubMed1993

Heteroplasmy in Leber's hereditary optic neuropathy.

OBJECTIVES: To determine the incidence and clinical significance of peripheral blood heteroplasmy and the presence of normal and mutant mitochondrial DNA in Leber's hereditary optic neuropathy through evaluation of a large series of families with the 11778 mutation and to evaluate the pattern of transmission of heteroplasmy. DESIGN: We studied heteroplasmy in 75 visually symptomatic patients with the 11778 mutation and in 101 asymptomatic family members. We compared the incidence of heteroplasmy in these two groups, collected clinical information for each symptomatic patient, and calculated the incidence of heteroplasmy within each generation of the pedigrees. RESULTS: We detected heteroplasmy in 24 (14%) of the 176 persons tested. Kaplan-Meier life-table analysis suggests that heteroplasmic persons are more likely to remain asymptomatic than those who are homoplasmic mutant (males, P = .17; females, P = .14). However, heteroplasmic persons who become symptomatic do not seem to differ clinically from symptomatic patients who are homoplasmic mutant. Pedigree analysis reveals a strong tendency for progression from heteroplasmy toward homoplasmy in subsequent generations (P = .001). CONCLUSION: Heteroplasmy for the 11778 mutation seems to play a role in the clinical expression of Leber's hereditary optic neuropathy and tends to progress toward homoplasmy in successive generations.

Adolescent↗
PubMed1993

Identical twins who are discordant for Leber's hereditary optic neuropathy.

OBJECTIVE: Leber's hereditary optic neuropathy is a maternally inherited form of visual loss that is associated with several mitochondrial DNA mutations. These mitochondrial DNA mutations are not the sole determinants of visual loss, as epigenetic factors may play a pathogenetic role. To clarify the role of these factors, we studied two visually discordant twins and determined their zygosity and mitochondrial genotype. DESIGN: Case series. SETTING: Referral center. PATIENTS: Identical twin brothers from a family with the 11778 mitochondrial DNA mutation. MAIN OUTCOME MEASURES: Visual acuity, results of testing for visual fields (measured with static and dynamic perimetry) and color vision, and results of funduscopic examination; alcohol and tobacco use, head trauma, co-existent medical illness, and occupational exposure; and results of mitochondrial DNA analysis and determination of zygosity. RESULTS: The monozygous twin brothers have remained discordant for the development of optic neuropathy for 6 1/2 years despite harboring the identical homoplasmic 4216, 13708, and 11778 mitochondrial DNA mutations. CONCLUSIONS: The patients are visually discordant despite being genetically identical at the nuclear and mitochondrial levels. Epigenetic factors are important determinants of visual loss in Leber's hereditary optic neuropathy in these brothers. Among those factors studied in these patients, a substantial difference was noted in regard to occupational exposure to toxic substances. Epigenetic factors that may influence the clinical expression of the mitochondrial DNA mutations associated with Leber's hereditary optic neuropathy should be systematically studied. Risk-factor intervention strategies should be formulated and implemented.

Adult↗
PubMed1993

Alveolar rhabdomyosarcoma that metastasized to the orbit.

A 22-year-old woman with a history of hyperthyroidism and a paravaginal alveolar rhabdomyosarcoma developed diplopia 3 months after successful autologous bone marrow transplantation. Results of computed tomographic scan showed apparent enlargement of the right inferior rectus muscle, and thyroid eye disease was suspected. However, results of further evaluation revealed an alveolar rhabdomyosarcoma that metastasized to the orbit.

Adult↗
PubMed1993

Primary adenocarcinoma of the lacrimal gland. A retrospective study.

BACKGROUND: Primary adenocarcinoma of the lacrimal gland is rare and usually appears in the literature as case reports. The authors retrospectively studied cases of primary adenocarcinoma of the lacrimal gland to determine which of the currently used methods was most effective in treating this tumor. METHODS: The authors requested cases of primary adenocarcinoma of the lacrimal gland from orbital surgeons and ocular pathologists worldwide. Of the cases referred, 13 examples of primary adenocarcinoma of the lacrimal gland could be confirmed and studied for clinical features, management, and outcome. RESULTS: The authors have follow-up data on all 13 patients. Six patients died of cancer, three are alive with recurrence, and four are alive and disease-free. CONCLUSION: Based on the results of this study, the authors ascertain that primary adenocarcinoma of the lacrimal gland is not inevitably fatal and should be treated with exenteration and adjuvant radiotherapy as soon as a histologic diagnosis is established. Shorter duration of symptoms before treatment appears to decrease the chance of metastases and increase the chance of long-term survival.

Adenocarcinoma↗
PubMed1993

Leber's hereditary optic neuropathy. Clinical manifestations of the 15257 mutation.

BACKGROUND: Leber's hereditary optic neuropathy is associated with four known pathogenetic mutations of mitochondrial DNA (mtDNA) at nucleotide positions (np) 11778, 3460, 15257, and 14484. METHODS: The authors collected clinical data from 12 visually symptomatic patients from seven different pedigrees with the 15257 mutation and compared these data with previously published clinical features of the 11778 and 3460 mutations. RESULTS: The authors' results indicate that these three groups of patients are similar in most clinical characteristics evaluated. However, patients with the 15257 mutation are more likely to experience significant recovery of visual acuity than patients with the 11778 mutation (25% versus 4% of eyes; P < 0.001). Patients with the 15257 mutation who also have an associated mutation at np 15812 are less likely to recover vision than those without this association (P = 0.001). Patients with the 15257 mutation also have a higher incidence of spinal cord and peripheral neurologic symptoms (42%) than patients with the other pathogenetic mutations. CONCLUSIONS: The phenotypic expression of the 15257 mutation differs from the 11778 and 3460 mutations and is affected by the presence of an associated mutation at np 15812. This is the first clinical evidence to support the concept of multiple simultaneous mtDNA mutations producing additive deleterious effects in patients with Leber's hereditary optic neuropathy. The clinical differences between the various genotypes associated with Leber's hereditary optic neuropathy have implications for risk factor management and visual prognosis and, thus, underscore the importance of molecular genetic testing in patients with suspected Leber's hereditary optic neuropathy.

Adolescent↗
PubMed1993

Oil-drop cataracts.

The oil-drop cataract is a common yet often overlooked cause of progressive vision loss. Although the nuclear change can be subtle on slitlamp biomicroscopic examination, retinoscopy reveals the classic oil droplet silhouetted against the red reflex. We present seven patients with oil-drop cataracts referred for neuro-ophthalmologic evaluation because of unexplained vision loss. All had been evaluated by multiple physicians and had had extensive diagnostic testing. The patients were between 36 and 69 years old with visual acuities from 20/20 to 20/400. The neuro-ophthalmologic evaluation in all patients was normal except for lenticular nuclear changes, best appreciated with retinoscopy.

Adult↗
PubMed1993

Novel brainstem syndrome associated with prostate carcinoma.

Two patients successfully treated for prostatic cancer developed a progressive neurologic syndrome beginning with loss of voluntary horizontal eye movements followed by severe, persistent muscle spasms of the face, jaw, and pharynx. Both had mild gait unsteadiness, and one exhibited facial and abdominal myoclonus. Extensive diagnostic studies, including MRIs of the brainstem (with and without contrast), were normal. CSF examination showed mild pleocytosis and elevated IgG. Quantitative eye movement recordings documented selective involvement of voluntary horizontal saccades with sparing of horizontal slow eye movements. Neither patient had antineuronal antibodies in the blood. Postmortem examination revealed perivascular chronic inflammatory cells and microglial infiltration of the pons and medulla. One patient also had perivascular infiltrates in both mesial temporal lobes. Neuronal loss was localized to the pontine tegmentum, the medullary sensory nuclei, and the cerebellum. Brainstem motor nuclei were preserved. The clinical and pathologic findings suggest an autoimmune process (probably paraneoplastic) with selective damage to a subpopulation of brainstem neurons critical for horizontal eye movements and recurrent inhibition of bulbar nuclei.

Adenocarcinoma↗
PubMed1993

Glioblastoma multiforme masquerading as pseudotumor cerebri. Case report.

A 16-year-old girl developed headaches and bilateral papilledema while taking minocycline for acne. The initial neuro-ophthalmologic evaluation was normal except for enlarged blind spots OU. An MRI scan demonstrated subtle abnormalities. A lumbar puncture was entirely normal except for an increased opening pressure. A tentative diagnosis of pseudotumor cerebri was made and the patient was treated with Diamox. A second MRI was unchanged, and a lumbar puncture performed while the patient was taking Diamox was entirely normal. The patient subsequently lost vision in both eyes, and a third MRI now revealed a supracellar enhancing mass. Biopsy and subtotal resection of the mass showed it to be a glioblastoma multiforme. This case emphasizes pitfalls in the diagnosis of pseudotumor cerebri. Careful follow-up and a high index of suspicion in pseudotumor cerebri syndromes are essential.

Adolescent↗
PubMed1992

Ophthalmic involvement in myo-neuro-gastrointestinal encephalopathy syndrome.

We studied the clinical, histopathologic, neuroradiologic, biochemical, and genetic profile of a patient with the myo-neuro-gastrointestinal encephalopathy syndrome, a recently described multisystem mitochondriopathy characterized by blepharoptosis and ophthalmoparesis. The patient had severe intestinal pseudo-obstruction and a mixed demyelinating and axonal neuropathy. Abnormal collections of mitochondria in nerve and muscle as well as diffuse white matter disease were present. Cytochrome oxidase activity in muscle mitochondria was reduced. No mitochondrial DNA deletions were detected.

Adult↗
PubMed1992

A randomized, controlled trial of corticosteroids in the treatment of acute optic neuritis. The Optic Neuritis Study Group.

BACKGROUND AND METHODS: The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. RESULTS: Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did not differ from that in the placebo group. In addition, the rate of new episodes of optic neuritis in either eye was higher in the group receiving oral prednisone, but not the group receiving intravenous methylprednisolone, than in the placebo group (relative risk for oral prednisone vs. placebo, 1.79; 95 percent confidence interval, 1.08 to 2.95). CONCLUSIONS: Intravenous methylprednisolone followed by oral prednisone speeds the recovery of visual loss due to optic neuritis and results in slightly better vision at six months. Oral prednisone alone, as prescribed in this study, is an ineffective treatment and increases the risk of new episodes of optic neuritis.

Acute Disease↗
PubMed1992

Leber's hereditary optic neuropathy. Clinical manifestations of the 3460 mutation.

Leber's hereditary optic neuropathy is associated with three different point mutations of mitochondrial DNA that appear to be pathogenetic for the disease. These mutations affect nucleotide positions 3460, 11,778, and 15,257. We reviewed the clinical characteristics of 12 visually symptomatic patients from nine families with the 3460 mutation and compared them with previously published characteristics of symptomatic patients with the 11,778 mutation. The patients with the 3460 mutation were similar to the patients with the 11,778 mutation in most clinical parameters. However, the patients with the 3460 mutation had a higher incidence of visual recovery (20% vs 4%, P = .001), a higher percentage of pedigrees with more than one affected family member (78% vs 43%, P = .011), and a greater frequency of tobacco and alcohol abuse. The difference in visual prognosis between these two mutations and the need for modification of possible risk factors provide added significance to genetic testing for Leber's hereditary optic neuropathy.

Adolescent↗
PubMed1992

Diagnosis of cavernous sinus arteriovenous fistula by measurement of ocular pulse amplitude.

BACKGROUND: The ocular pulse amplitude (OPA), the difference between the maximum and minimum intraocular pressure (IOP) during the cardiac cycle, has been reported to be elevated in the eye ipsilateral to a cavernous sinus arteriovenous fistula. METHODS: The OPA was measured with a pneumotonometer in three groups of patients. Patients in group 1 had no orbital disease (n = 50), patients in group 2 had either unilateral or asymmetric orbital disease (n = 30), and patients in group 3 had angiographically proven cavernous sinus arteriovenous fistulas (n = 15). RESULTS: Patients in group 3 had a higher OPA than patients in either group 1 (P less than 0.001) or group 2 (P less than 0.001). The difference in OPA between an individual's eyes (delta OPA) also was higher in patients with cavernous sinus arteriovenous fistulas than in patients without fistulas (P less than 0.0001). CONCLUSION: A delta OPA of more than 1.6 mmHg was 100% sensitive and 93% specific in identifying patients with cavernous sinus arteriovenous fistulas. There was no difference in delta OPA between direct and dural cavernous sinus arteriovenous fistulas. Successful transvascular embolization of the cavernous sinus arteriovenous fistula normalized the delta OPA by reducing the OPA on the affected side.

Adult↗