[Pitfalls in the diagnosis of benign paroxysmal positional vertigo].

Benign paroxysmal positional vertigo (BPPV) is a common but often unrecognized cause of treatable vertigo. Possible causes of misdiagnosis of BPPV were studied by review of the records of 191 patients referred to our neurology clinic; 36 were identified as having BPPV not previously diagnosed. On referral the patients carried the following diagnoses: unspecified dizziness/vertigo (33%), transient ischemic attacks (28%), cervicogenic vertigo (19%), psychogenic dizziness/vertigo (11%), and others (8%). The paroxysmal nature of the vertigo and position-precipitating factors were not spontaneously reported by 31%. Atypical, even bizarre, symptoms including dizzy sensations were reported by 19%, and neck pain and headache were cardinal symptoms that accompanied vertigo. The Dix-Hallpike maneuver, which is essential for the diagnosis of BPPV, was not performed in any of the patients prior to referral. 30 (83%) experienced complete resolution of signs and symptoms after the first physical treatment session. We conclude that non-paroxysmal, non-positional vertigo does not rule out BPPV. Atypical and even bizarre complaints of dizziness, as well as neck pain and headache could be cardinal symptoms of BPPV. The Dix-Hallpike maneuver is mandatory in those complaining of dizziness and vertigo.

Value of prothrombin fragment 1.2 (F 1.2) in the diagnosis of stroke in young patients with antiphospholipid antibodies.

The presence in the serum of antiphospholipid antibodies (aPL) is associated with venous and arterial thrombosis. This observation has led to the search for these antibodies in young patients with ischemic neurologic syndromes. However, 1% to 5% of healthy people may be found to have circulating aPL without necessarily being at increased risk of thromboembolism. Thus, the finding of APLA in a patient with cerebral ischemia does not necessarily provide an explanation for the etiology of the clinical syndrome. The aim of this study was to determine whether the presence of aPL in young patients with stroke or transient ischemic attacks represents a possible cause of hypercoagulability as defined by ongoing thrombin formation with resultant elevation of prothrombin fragment 1.2 (F1.2) levels. This was a retrospective, case-control study involving 57 subjects. Twenty-seven patients had a recent cerebrovascular ischemic event--either TIA or a stroke. Fifteen were positive for aPL, and 12 were aPL-negative. Thirty subjects, matched for age and sex with no history of cerebrovascular disease, served as controls. Of this group, 20 were aPL-positive and 10 were aPL-negative. Causes of hypercoagulability other than aPL were excluded by laboratory testing. A positive test for aPL was repeated after a 6-week interval and two positive tests were required for a patient to be regarded as being aPL-positive. Levels of F1.2 were measured by an ELISA technique. There was a significant difference (p < 0.05) in the mean F1.2 levels between the aPL-positive group with a history of cerebrovascular disease (mean F1.2 = 2.3733) and each of the other study groups. There was no statistically significant difference between any of the other study groups. Our findings suggest that F1.2 levels are elevated in young patients with cerebrovascular syndromes who have aPL and in whom other causes of hypercoagulability and atherosclerotic vascular disease are absent. Elevated F1.2 in these patients may be a potential marker of the hypercoagulable state associated with aPL.

Idiopathic intracranial hypertension and anticardiolipin antibodies.

The association of idiopathic intracranial hypertension (IIH) or pseudotumour cerebri (PTC) with anticardiolipin antibodies (aCL-Abs) has been only acknowledged recently. However, its true incidence is as yet unknown. In this retrospective study, the co-occurrence of IIH and aCL-Abs was looked for among a relatively large group of patients diagnosed with IIH or PTC in the neuro-ophthalmology clinic during the years of 1992-8. All patients underwent routine blood tests and the presence of activated protein C resistance and protein S and protein C deficiency were recorded. ACL-Abs were determined in all patients. The co-occurrence of IIH and aCL-Abs was found in three out of 37 patients (8.1%), which is higher than the incidence of aCL-Abs in the general population but considerably lower than that reported in two previously published studies. The aCL-Ab positive patients in our series were significantly older and thinner than those in whom antibodies were undetected. In conclusion, it seems that patients with this association should be considered as a unique subgroup of IIH.

Transmission of HTLV-I to rats via peripheral blood mononuclear cells and serum from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) with amyotrophic lateral sclerosis (ALS)-like features.

We tested the possibility that lymphocytes and serum obtained directly from a patient with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) induce infection in rats. Inbred Fischer F344 immunosuppressed rats were inoculated intravenously with 10x10(6) peripheral blood mononuclear cells (PBMC; 3 rats) and serum (3 rats) obtained from a HAM/TSP patient, who was seropositive and polymerase chain reaction (PCR)-positive for the HTLV-I proviral genome. Antibodies to HTLV-I appeared in the rat sera 2 months later; rat peripheral blood lymphocytes, spleen, salivary gland, and spinal cord were found to contain the proviral genome. Control rats inoculated with normal donor PBMC and serum tested negative for the HTLV-I antibodies and for the HTLV-I proviral genome by PCR. The positive control F344 rats inoculated with 5x10(6) cells of a SLB-1 HTLV-I cell line were found to be infected after 2 months. This study demonstrates for the first time that HTLV-I can be transmitted not only by human cellular components but also by human cell-free sera in a rat model.

In vivo 23Na NMR studies of myotonic dystrophy.

Myotonic dystrophy is an inherited multi-system disease. Its pathophysiology leading to muscle malfunction and damage is not well understood. 23Na NMR spectroscopy was applied here for an in vivo comparative study of the calf muscles of 7 myotonic dystrophy patients at various stages of the disease and 11 healthy volunteers. Both the total sodium content, expressed as the ratio of the 23Na and 1H water signals, and the fast transverse relaxation time, T2f, determined from the triple quantum-filtered spectra, increased in correlation with the severity of the disease. The results demonstrate that 23Na NMR enables the quantitation of myotonic dystrophy progression.

[Post-shock optic neuropathy].

A case of rare, post-shock optic neuropathy is presented. In most cases, it occurs after blood loss or decrease in blood pressure. We present a woman, aged 47, with this condition in whom 3 possible causes, hypoxia, hypercoagulability and vasodilatation, coexisted. Neurologists and ophthalmologists should be aware of this rare condition, because prompt treatment with steroids and hemodynamic stabilization may significantly improve outcome.

[Optic nerve sheath enlargement and reversal of optic nerve head in pseudotumor cerebri].

Using standard cerebral computerized tomography (CT), we diagnosed pseudotumor cerebri (PTC) and correlated the CT findings with CSF pressure and severity of visual impairment. 13 patients with a clinical diagnosis of PTC were compared with 20 age-matched controls with headache, but without papilledema or other neurologic signs. Cerebral CT consisted of axial sections of the posterior fossa, including the orbits. In all subjects the diameter of the optic nerve sheath, reversal of the optic nerve head, presence of empty sella, and size of the ventricles, cisterns and sulci were evaluated. There were no differences in basal cisterns and ventricles between those with PTC and control subjects. Empty sella was found in 6 of 13 PTC patients, compared with 1 of the 20 controls. Optic nerve sheath diameter in controls ranged from 3.5-5.0 mm (average 4.2 +/- 0.54 mm) but from 4.5-9.0 mm (average 6.8 +/- 1.54 mm) in those with PTC. Reversal of the optic nerve head was seen in 4 cases of PTC but in none of the controls. In PTC patients with opening CSF pressure greater than 270 mm water, the diameter of the optic nerve was wider than 7.5 mm. Thus, in most cases of PTC, bilateral enlarged optic nerves can be measured by standard cerebral CT and intracranial space-occupying lesions can be excluded as well. Moreover, reversal of optic nerve head, and empty sella can frequently be seen on CT in those with PTC.

Slowly progressive aphasia, a left temporal variant of probable Pick's disease: 15 years of follow-up.

It is known that word-finding difficulties or anomia are the first signs observed in Pick's disease. We report a 15 year follow-up of a woman who at the age of 52 suddenly developed a speech impairment and only 6 years later showed other cognitive disturbances compatible with Pick's disease. This case demonstrates that nonfluent aphasia and agrammatic aphasia may constitute the first signs of this disease, stressing the importance of prolonged follow-up in such cases.

T lymphocyte subpopulations and activation markers correlate with severity of Alzheimer's disease.

In this study we investigated immune-associated antigens of peripheral lymphocytes from patients with Alzheimer's disease (AD). The patients were divided into two groups--mild and moderately severe--according to severity of disease stage, and their lymphocytes were compared to those of elderly controls. In the mild stage of the disease we observed a slight increase in the HLA-DR marker (9.5 +/- 2.4% vs 6.5 +/- 1.1%; P = 0.06), but no changes in the CD4, CD8, and interleukin-2 receptor (IL-2R) markers. In the moderately severe stage, we observed a significant increase in the HLA-DR (18.5 +/- 2.7%) and CD4 markers (55.2 +/- 3.5% vs 43.5 +/- 2.1%, P < 0.01), and a slight decrease in the CD8 subset (19.5 +/- 1.4% vs 22.3 +/- 1.3%, P = 0.05). In the same group, following stimulation with the mitogen PHA, we observed a marked reduction in IL-2R expression (30.9 +/- 4.7% vs 41.1 +/- 2.7%, P = 0.05) and in the proliferative ability of lymphocytes (21131 +/- 4676 cpm vs 47909 +/- 1107 cpm, P < 0.04). However, mitogen-induced IL-2 secretion levels from the same lymphocytes were significantly elevated (17.4 +/- 4.8 U/ml vs 8.6 +/- 4.3 U/ml, P < 0.01). Marked changes in immunological parameters in the moderately severe group support the hypothesis of a peripheral immune reaction in AD which may be correlated with the clinical stage of the disease.

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease.

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups--mild and moderately-severe--according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.

Fibrosing alveolitis associated with primary antiphospholipid syndrome.

The spectrum of the primary antiphospholipid syndrome has expanded in recent years. It has been associated with a number of non-thrombotic syndromes such as pulmonary hypertension, adrenal insufficiency, chorea and avascular necrosis of bone. Yet, it has not been described in association with inflammatory pulmonary disease. We describe a young male with definite primary antiphospholipid syndrome who developed insidious diffuse pulmonary infiltrates. The histopathologic examination of the involved lung demonstrated alveolitis and fibrosis. We suggest that this pulmonary involvement may represent another manifestation of the primary antiphospholipid syndrome.

Correlation of cytokine secretion by mononuclear cells of Alzheimer patients and their disease stage.

Cytokine secretion by human mononuclear cells (MNC) was investigated in age-matched controls and in patients with Alzheimer's disease (AD). AD patients were divided into two study groups: 'mild' and 'moderately severe'. A significant increase in interleukin-2 (IL-2) and gamma interferon (IFN-gamma) secretion was found in AD patients in the moderately severe stage of the disease, whereas in the mild stage of the disease there was a significant decrease in interleukin-3 activity (IL-3) and tumor necrosis factor (TNF) levels. No significant differences were found in the level of production of interleukin-1 (IL-1 beta). Our results demonstrate the existence of defective immune functions in AD patients which are correlated with the clinical condition of these patients.

Elevated interleukin-6 secretion levels by mononuclear cells of Alzheimer's patients.

It has been suggested in recent research that interleukin-1 (IL-1) and interleukin-6 (IL-6) play a role in the pathogenesis of Alzheimer's disease (AD). Production of IL-1, by lipopolysaccharide (LPS)-stimulated monocytes, and IL-6, by phytohaemagglutinin (PHA)-stimulated mononuclear cells, was assessed in patients with AD divided into two groups--mild and moderately severe--according to severity of disease, and elderly controls. No differences in IL-1 production were found among AD patients and controls. However, significant elevation in IL-6 secretion levels was observed in both the mild and moderately severe AD patients. Our results suggest that peripheral IL-6 secretion levels may be responsible for acute-phase proteins observed in the serum of AD patients.

Myasthenia gravis: rarity of gallstone formation.

There is an increase in the production of gallbladder stones (cholelithiasis) following gastrectomy associated with vagotomy; we hypothesized that in the presence of constant stimulation of the vagal system, there should be decreased production of gallstones. Forty-two myasthenia gravis patients taking continuous anticholinesterase medications underwent ultrasound study of the gallbladder; only one patient, aged 62, had gallstones. In the control group of 112 nonmyasthenics matched for age and ethnic origin, 45 had stones. This study suggests that cholinergic medications protect against gallstones.

Decreased IL-3 production by peripheral blood mononuclear cells in patients with multiple sclerosis.

The production of interleukin-3 by peripheral blood mononuclear cells (MNC) was assessed in patients with relapsing multiple sclerosis (MS) in both the active and the stable state, and in healthy controls. IL-3 levels were compared to levels of production of interleukin-2 (IL-2), tumor necrosis factor (TNF) and gamma-interferon (gamma-IFN). No significant differences in IL-3 levels were observed between stable-state patients and controls. When levels of cytokine production of patients in the inactive phase were compared to those of the same patients during relapse a significant decrease in IL-3 levels was observed, as opposed to significant increases in gamma-IFN and TNF levels, and an increase, though a non-significant, in IL-2 levels. The functional significance of lowered IL-3 production is unknown. However, the findings support the hypothesis of a highly complex interaction of overlapping regulatory influences within the cytokine network which parallels MS disease activity.

[Septic cavernous sinus thrombosis].

Septic cavernous sinus thrombosis is a rare complication of facial infections, particularly of the dangerous triangle (nose and upper lip) and less often of the orbit, middle ear, pharynx or teeth. Staphylococcus aureus is the most frequent causative agent. Prompt diagnosis and early aggressive antibiotic therapy, with or without anticoagulants, is required. A 49-year-old woman developed this complication following multiple nasal abscesses. Despite intensive antibiotic and anticoagulant therapy she became permanently blind. We present this case to stress the fact that this disease is still fraught with high morbidity, and even mortality.

Interferon system and natural killer cell activity in myasthenia gravis.

The autoimmune response in myasthenia gravis is well characterized, but little is known about the mechanisms initiating it. We have studied the interferon system and natural killer cell activity in 25 patients with myasthenia gravis and compared them to 68 healthy subjects and 96 patients with acute viral infections. Forty-four per cent of patients had circulating interferon (greater than 16 mu/ml), and in a similar proportion their peripheral blood mononuclear cells were in an antiviral state, i.e., showed low levels of viral replication when infected by vesicular stomatitis virus. Spontaneous in vitro interferon production by patients' peripheral blood mononuclear cells was also common (greater than 10 mu/ml, 32 per cent), while the response to the alpha-interferon inducer poly I:C was lower than expected, possibly reflecting the already high state of activation of the interferon system. These results were essentially similar to those obtained in patients with viral illnesses and differed significantly from healthy controls. In many myasthenia gravis patients (16 of 22, 73 per cent), a markedly deficient natural killer cell activity was found, with a median cytotoxicity of 6.5 per cent compared to 29 per cent in healthy subjects (p less than 0.005). Thus, many patients with myasthenia gravis have evidence of an activated interferon system and defective natural killer cell activity, suggesting an occult viral infection or reflecting nonspecific stimulation which may nevertheless contribute to the pathogenesis of the autoimmune response.

The interferon system in subacute sclerosing panencephalitis and its response to isoprinosine.

Plasma interferon activity (IFN) and its spontaneous and stimulated production by peripheral blood mononuclear cells (PBMC) was studied in 11 patients with subacute sclerosing panencephalitis (SSPE) and age-matched healthy controls. The patients, similar to the healthy controls, had no detectable plasma IFN activity. However, their PBMC failed to produce IFN in response to stimulation with poly I:C and PHA. After isoprinosine administration to 7 patients for several days a significant increase in plasma IFN activity was observed and their PBMC responded to stimulation by producing IFN. The long-term effect of isoprinosine on the IFN response was evaluated in 3 patients who had been treated for 57-88 days. Induction of the abolished IFN production was observed with initiation of therapy. However, discontinuation of isoprinosine for 10 days resulted in recurrence of the inactivation state of the IFN system.