Vocal fold paresis - a debilitating and underdiagnosed condition.

OBJECTIVES: To review the clinical signs of vocal fold paresis on laryngeal videostroboscopy, to quantify its impact on patients' quality of life and to confirm the benefit of laryngeal electromyography in its diagnosis. METHODS: Twenty-nine vocal fold paresis patients were referred for laryngeal electromyography. Voice Handicap Index 10 results were compared to 43 patients diagnosed with vocal fold paralysis. Laryngeal videostroboscopy analysis was conducted to determine side of paresis. RESULTS: Blinded laryngeal electromyography confirmed vocal fold paresis in 92.6 per cent of cases, with vocal fold lag being the most common diagnostic sign. The laryngology team accurately predicted side of paresis in 76 per cent of cases. Total Voice Handicap Index 10 responses were not significantly different between vocal fold paralysis and vocal fold paresis groups (26.08 ± 0.21 and 22.93 ± 0.17, respectively). CONCLUSION: Vocal fold paresis has a significant impact on quality of life. This study shows that laryngeal electromyography is an important diagnostic tool. Patients with persisting dysphonia and apparently normal vocal fold movement, who fail to respond to appropriate speech therapy, should be investigated for a diagnosis of vocal fold paresis.

Spasmodic dysphonia: clinical features and effects of botulinum toxin therapy in 169 patients-an Australian experience.

Adductor spasmodic dysphonia (SD) is a focal laryngeal dystonia, characterised by strangled, effortful speech with breaks in pitch and phonation. Injection of laryngeal muscles with BTX is widely used in the treatment of SD. A consecutive series of 169 patients with SD, of whom 144 were treated with BTX injections, seen at St. Vincent's Hospital between 1983 and 1999 were studied prospectively. Patients underwent neurological, quantitative voice and otolaryngological assessment. Females (62.1%) outnumbered males (37.9%) and the mean age at diagnosis was 56 years (range 19-88). Adductor SD (89.4%) was more frequent than abductor SD (1.8%) or mixed SD (4.7%). Stridor was present in 14 patients (8.3%) and in 7 was the sole manifestation of the laryngeal dystonia. The median treatment outcome score was excellent in 63.2%, very good in 18.5%, satisfactory in 14.7% and unsatisfactory in 3.5%. Poorer treatment outcome was associated with abductor SD (OR = 4.69, CI [1.23, 17.92] p=0.024] and age >65 (OR = 2.83, CI [0.95, 8.42] p=0.049). Mild post-injection paralytic dysphonia was associated with longer lasting treatment (4.42 vs. 3.62 months p<0.001) and superior treatment outcome rating (1.37 vs. 1.81 p<0.001). We conclude that BTX injections are highly effective and severe adverse events are rare. Older age and abductor SD may confer a relatively poorer treatment outcome. Mild post-injection paralytic dysphonia may be a marker for more effective and lasting treatment in adductor SD.

Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patient with AIDS.

Microsporidia are zoonotic protozoa which were rare human pathogens prior to 1985, when Enterocytozoon bieneusi was described in human immunodeficiency virus-infected patients with chronic diarrhea. Another species, Encephalitozoon (Septata) intestinalis, is associated with diarrhea and chronic sinusitis, and approximately 25 cases have been reported in the literature. However, other microsporidial infections in human immunodeficiency virus-infected patients remain extremely rare. We report the first case of a Pleistophora sp.-like microsporidian infection presenting as a progressive severe myosotis associated with fever and weight loss. The organism was demonstrated by light microscopy and electron microscopy in corneal scrapings, skeletal muscle, and nasal discharge. Electron microscopy showed an electron-dense surface coat with "sunflare"-like projections surrounding all stages of development of meronts (two to four nuclei, dividing by binary fission), sporonts, and sporoblasts. Division of sporonts, in which sporonts separate from the thick outer coat, creating a sporophorous vesicle, is by binary fission, differentiating this organism from Pleistophora sp. The spore measures 4.0 by 2.5 microns and has a rugose exospore. A new genus and species, Trachipleistophora hominis, has been established for this parasite. The patient was treated with albendazole, sulfadiazine, and pyrimethamine, and the clinical symptoms resolved.

Heat stroke following Rugby League football.

OBJECTIVE: To present a case of severe heat stroke after Rugby League football. CLINICAL FEATURES: A 29-year-old Rugby League forward with a mild infection of the upper respiratory tract collapsed while playing football in late March, when the ambient temperature was 24.1 degrees C and the relative humidity up to 73%. He was initially thought to have sustained a head injury and was markedly dehydrated. He suffered severe disseminated intravascular coagulation and gross neurological, renal and hepatic disturbances. INTERVENTION AND OUTCOME: He required repeated haemodialysis, assisted ventilation and supportive therapy and remained unconscious for 10 days. He then recovered fully. CONCLUSION: Heat stroke is potentially fatal and can be easily mistaken for head injury in contact sports. When players are dehydrated, have febrile illness and play in warm conditions, they may succumb to heat stroke.

The neurological features of early and 'latent' human immunodeficiency virus infection.

Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.

A review of 20 cases of spastic dysphonia.

Twenty patients with the distinct nosological entity of adductor spastic dysphonia (SD) were seen at St Vincent's Hospital, Sydney over a 6-year period. Nine of these patients also experienced a tremulous voice associated with evidence of an essential tremor (ET) elsewhere, including head, trunk and limbs. The mean age of onset in patients with SD was 45 years and in those with SD with ET was 52 years. In 10 patients the onset was gradual, with the remaining 10 experiencing an abrupt onset, in 3 related to an upper respiratory tract infection and in 7 to psychosocial stress. Factors which frequently resulted in a worsening of speech included stress, public speaking, tiredness, strong emotions, upper respiratory tract infections and prolonged use of the voice. In patients with SD alone temporary relieving factors included spontaneous statements, use of a quiet voice, slow speech, high and low pitch, yawning, chewing, swallowing, laughing and on first waking in the morning. The response to therapy was variable. Two patients underwent recurrent laryngeal nerve sectioning.

Adductor spastic dysphonia: heterogeneity of physiologic and phonatory characteristics.

Physiologic and phonatory characteristics of 23 subjects with adductor spastic dysphonia were studied, including examination of the laryngeal appearance by fiberoptic nasoendoscopy, neurologic examination, and measurement of phonatory airflow and speaking fundamental frequency. These characteristics displayed considerable heterogeneity among the subjects investigated. Three patterns of laryngeal appearance during phonation were observed: vocal fold adduction, associated ventricular fold constriction, and approximation of the laryngeal inlet. Eight of 13 subjects demonstrated some neurologic abnormality. For the majority of subjects, the airflow demonstrated marked variability during sustained phonation; for different subjects, this variability was observed to be associated with either an oscillatory or irregular airflow pattern. The modal speaking fundamental frequency for the women and men with adductor spastic dysphonia was not significantly different from that for age- and sex-matched controls.

Neoplastic angioendotheliosis.

Neoplastic angioendotheliosis is a rare disease in which malignant cells are found within numerous blood vessels throughout the body in the absence of any detectable extravascular primary malignancy. The disorder has a propensity for clinical neurological involvement despite pathological evidence of systemic spread. To date 23 patients with neurological involvement have been described. This report adds a further 3 cases. There was no definite evidence to support the theory that the malignancy arises in endothelial cells; no primary extravascular tumour was found. At present a definite conclusion about the cause of the disease cannot be made.

Cyclosporin-associated central nervous system toxicity after allogeneic bone marrow transplantation.

Five of 64 recipients of HLA-identical sibling marrow allografts who were given cyclosporin (CSP) to minimize graft-versus-host disease posttransplant had a serious neurological illness thought to be due to CSP. Characteristic clinical features included a motor spinal cord syndrome, a cerebellar-like syndrome, and mental confusion. All five recovered when the CSP dose was reduced or the drug was stopped.

Tissue distribution and toxicity of cyclosporin A in the mouse.

Groups of mice were given cyclosporin A (CyA) subcutaneously for 6 wk at a dose of 12.5, 50 or 200 mg/kg/d. After 7, 21 and 42 days of CyA administration the CyA content of serum, thymus, mesenteric lymph nodes, spleen, kidney, liver, lung, small and large intestine and brain was measured, each organ was examined histologically, and the total viable nucleated cell content of thymus, mesenteric lymph nodes, spleen and femoral marrow was analysed. CyA was detected in every organ assayed at each concentration of CyA administered. The mean concentration of CyA per organ was consistently highest in organs of mice given CyA 200 mg/kg/d and lowest in those given 12.5 mg/kg/d at each time point, but there was pronounced variability in the concentration of CyA between individual mice. Repeated administration of CyA after the first week did not further elevate CyA tissue concentrations. At doses of 50 or 200 mg/kg/d CyA caused weight loss, diarrhea, intussusception and fatal neurotoxicity. In addition, the spleen, thymus and mesenteric lymph nodes of mice given CyA 50 or 200 mg/kg/d were hypocellular and disorganized, and all lymphoid organs contained numerous pyknotic lymphocytes. The liver showed fatty change and the kidney degeneration of proximal tubules. Femoral marrow showed enlarged and congested sinuses. No abnormalities were noted in mice given CyA 12.5 mg/kg/d.

Acute ischaemic neuropathy in the rabbit.

Ligation of either the common and internal iliac or the internal and external iliac arteries produced ischaemic lesions of the sciatic nerve and its branches, as well as direct muscle damage, in 5 out of 6 rabbits. In one animal, ligation of the aorta and of the internal iliac artery on one side produced a similar mixture of nerve and muscle damage on the side of the double ligation. Ligation of the femoral artery alone in 3 animals failed to produce significant changes. In the 6 affected animals there was paralysis of the hind leg on the side of the iliac ligations, with loss of tendon reflexes. Appreciation of pinprick over the foot and lower leg also appeared to be impaired. Complete ischaemic necrosis with irreversible damage to both neural and connective tissue elements did not occur in the main nerve trunks, but was present in some of the intramuscular nerve bundles as part of generalized coagulative necrosis of the most severely affected muscles. The characteristic pathological changes in the nerve fibres of the main nerve trunks were Wallerin degeneration and paranodal demyelination, the former being more extensive than the latter. In the animals with double iliac ligations, the upper level of ischaemic nerve damage was in the thigh, the tibial portion of the sciatic nerve being more commonly affected than the peroneal. Nerve and muscle damage tended to occur at different levels in the limb, but there was no example of clinical paresis due to neural damage without any ischaemic muscle changes being present. In two of the 3 animals in which the plantar muscles were examined, these muscles appeared to escape direct damage in spite of ischaemic lesions in the more proximal parts of the limb.

A mitochondrial myopathy with a deficiency of respiratory chain NADH-CoQ reductase activity.

This paper presents data on two sisters with a mitochondrial myopathy characterised by weakness, marked exercise intolerance and a fluctuating lactic acidaemia. Both patients also experienced episodes of increased weakness which could be brought on by unaccustomed activity, going without food or by taking small quantities of alcohol. Metabolic studies during exercise showed a marked and sudden rise in blood lactate and pyruvate levels. Biochemical studies in one case showed that mitochondrial respiratory rates were markedly decreased with all NAD-linked substrates tested but were normal with succinate and with TMPD + ascorbate. The mitochondrial cytochrome components were normal as determined by low temperature spectroscopy and the addition of uncoupler did not enhance state 3 respiratory rates utilising NAD-linked substrates. It was concluded, therefore, that the mitochondrial lesion was located at the level of the NADH-CoQ reductase complex.

Interaction of di-iodinated 125I-labelled alpha-bungarotoxin and reversible cholinergic ligands with intact synaptic acetylcholine receptors on isolated skeletal-muscle fibres from the rat.

1. Intact synaptic acetylcholine receptors on freshly isolated rat skeletal-muscle fibres were characterized by their interaction with di-iodinated 125I-labelled alpha-bungarotoxin, acetylcholine and other cholinergic ligands at room temperature (22 deggrees C). 2. The time course and concentration dependence of 125I-labelled alpha-bungarotoxin association conformed to a bimolecular mechanism. In time-course experiments with different concentrations of 125I-labelled alpha-bungarotoxin (1.4--200 nM) the bimolecular-association rate constant, k + 1, was (2.27 +/- 0.49) x 10(4)M-1.S-1 (mean +/- S.D., N = 10). In concentration-dependence experiments, k + 1 was 2.10 x 10(4)M-1.S-1 and 1.74 x 10(4) M-1.S-1 with 10 and 135 min incubations respectively. In association experiments the first-order rate constant was proportional to the 125I-labelled alpha-bungarotoxin concentration. 125I-Labelled alpha-bungarotoxin dissociation was first order with a dissociation constant, k-1, less than or equal to 3 x 10(-6)S(-1) (half-life greater than or equal to 60 h.) The results indicated a single class of high-affinity toxin-binding sites at the end-plate with an equilibrium dissociation constant, Kd, equal to or less than 100 pM. The number of toxin-binding sites was (3.62 +/- 0.46) x 10(7) (mean +/- S.D., n = 22) per rat end-plate. 3. The apparent inhibitor dissociation constants, Ki, for reversible cholinergic ligands were determined by studying their effect at equilibrium on the rate of 125I-labelled alpha-bungarotoxin binding. There was heterogeneity of binding sites for cholinergic ligands, which were independent and non-interacting with antagonists. In contrast agonist affinity decreased with increasing receptor occupancy. Cholinergic ligands in excess inhibited over 90% of 125I-labelled alpha-bungarotoxin binding. 4. Cholinergic ligand binding was accompanied by an increase in entropy, which was greater for the agonist carbachol (delta So = +0.46 kJ.mol-1.K-1) than the antagonist tubocurarine (delta So = +0.26 kJ.mol-1.K-1). 5. The entropy and affinity changes that accompanied agonist binding suggested that agonists induced significant conformational changes in intact acetylcholine receptors. 6. The affinity and specificity of 125I-labelled alpha-bungarotoxin and tubocurarine binding to synaptic acetylcholine receptors from slow and fast muscle fibres were the same. 7. The study of binding only requires milligram amounts of tissue and may have application to other neurobiological studies and to the study of human neuromuscular disorders.

Multiple progressive intracranial arterial occlusions ('moyamoya' disease).

Four adult female patients with moyamoya vessels are described. Hypertension and hyperlipidaemia were discovered in three patients. Vessels similar to moyamoya vessels were seen in the orbital and cortical collateral vessels as well as in the basal ganglia region. Attention should now be paid to the aetiological rather than the descriptive aspects of the disorder. An empirical trial of corticosteroids is worth while. Risk factors such as hypertension, hyperlipidaemia, and smoking should be eliminated.