Vestibular paroxysmia: vascular compression of the eighth nerve?

Ignorance of the HIV status of ex-donors means that there will be recipients, infected before 1985, who remain unidentified. In one recent investigation of a donor who stopped giving blood in 1984, 5 infected recipients have been identified. 2 were transfused in the early 1980s and were unaware that they were infected. The other 3 recipients had been identified as infected, but not notified to us. We have not been able to confirm the HIV infection in the donor, except on a balance of probabilities. The difficulty transfusion services face in the tracing of ex-donors infected with HIV is avoidable. If all HIV counselling and testing services were to ask individuals found to be infected with HIV if they have ever donated blood those answering in the affirmative could be requested to provide the date and location of the last donation. If those details are passed on to the blood transfusion service, with the individual’s consent, the fate of his or her donations could be traced and any infected recipients identified. In the UK such questioning is not routine. Furthermore, even when blood transfusion staff strongly suspect that an ex-donor is HIV infected they cannot confirm this because the reporting system coordinated by the PHLS Communicable Disease Surveillance Centre is confidential. We urge all HIV counselling and testing services to ask about blood donation whenever an individual is found to be infected with HIV. In our experience, former donors raise no objections to this information being passed to the transfusion centre, if the importance is clearly explained. Patricia E Hewitt National Blood Transfusion Service, North London Blood Transfusion Centre, London NW9 5BG, UK

received any blood product previously, and all were negative for serum markers for hepatitis B and HIV infection and had normal ALT levels. B 19 parvovirus antibodies were sought by capture radioimmunoassay3 and B19 DNA was tested for by nested PCR2 in sera collected before the first infusion and after 1, 2, 4, and 12 weeks. Haemoglobin was checked at the same times. 10 patients who were anti-Bl9 IgG negative before treatment were susceptible to parvovirus infection, and acute infection developed in 4 of them, as indicated by anti-Bl9 IgM 1-2 weeks after the first infusion followed by IgG seroconversion. Viral DNA was detected at the same time points. The B19 seroconverters had received 500, 1500, and 2000 IU of factor VIII and 4000 of factor IX from 4 distinct batches. About 2 weeks after the concentrate infusion, B19 infected patients showed a transient decrease in haemoglobin (0-7-2-2 g/dL) unrelated to any concomitant bleeding episodes. Their haemoglobin levels spontaneously recovered within a month of the infusion. Human parvovirus B19 was thus transmitted to susceptible patients despite the terminal heating of concentrates at 100°C for 30 min. Notwithstanding the limited clinical consequences of infection with parvovirus B 19, manufacturers of coagulation factor concentrates should look for alternative inactivation

strategies. E Santagostino, P M Mannucci, A

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2

Eliminating parvovirus B19 from blood products SiR-Using the polymerase chain reaction (PCR), Lefrere and colleagues (Jan 22, p 211) detected parvovirus B19 DNA in several batches of plasma-derived, large-pool coagulation factor concentrates virally inactivated with an organic solvent and a detergent. Similar observations were made by Zakvrzewska et al.1 Even though the presence of viral DNA does not prove infectivity, that the non-lipid-enveloped parvovirus B19 can infect patients with haemophilia given solvent/detergent treated concentrates is confirmed by the development of anti-B 19 IgM in their sera during the first two weeks after concentrate infusions.2 B19 infection can be symptomless or cause a benign and short-lived condition such as erythema, but in immunocompromised individual’s viraemia may persist and cause chronic anaemia.3 In an attempt to circumvent the lack of efficacy of solvent/detergent in inactivating parvovirus one Italian manufacturer (Aima Derivati) has recently chosen to add a terminal virucidal step based on heating at 100.C.4 To see if this robust method works, we did a prospective multicentre study in previously untreated patients infused for the first time with factor VIIIor IX concentrates that had been treated for 6 h with the lipid solvent tri(n-butyl)phosphate and the detergent Tween-80 and then heated for 30 min in the lyophilised state at 100°C. All plasma units used (at least 10000 per batch) were negative for hepatitis B surface antigen, hepatitis C virus antibody, and anti-HIV and had alanine aminotransferase (ALT) concentrations less than twice the upper normal limit. Fifteen batches of factor VIII and two of factor IX concentrates, totalling 80500 IU, were administered in 60 infusions to 17 patients (14 haemophilia A, 1 von Willebrand, 2 haemophilia B; median age 7 years, range 1-50). No patient had

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Gringeri, A Azzi, M Morfini

Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital and University of Milan, 20122 Milan, Italy; and Institute of Microbiology and Haemophilia Centre, University of Florence

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Zakvrzewska K, Azzi A, Patou G, Morfini M, Rafanelli D, Pattison JR. Human parvoviris B19 in clotting factor concentrates: B19 DNA detection by the nested polymerase chain reaction. Br J Haematol 1992; 81: 407-12. Azzi A, Ciappi S, Zakvrzewska K, Morfini M, Mariani G, Mannucci PM. Human parvovirus B19 infection in hemophiliacs first infused with two-purity, virally attenuated factor VIII concentrates. Am J Hematol 1992; 30: 228-30. Frickhofen N, Abkowitz JL, Safford M, et al. Persistent B19 parvovirus infection in patients infected with human immunodeficiency virus type 1 (HIV-1): a treatable cause of anemia in AIDS. Ann Intern Med 1990; 113: 926-33. Rubenstein AI, Rubenstein DB, Coughlin J. Combined solventdetergent and 100°C (boiling) sterilizing dry-heat treatment of factor VIII concentrates to assure sterility. Vox Sang 1991; 60: 60.

Vestibular paroxysmia: vascular compression of the eighth nerve? SIR—Neurovascular cross-compression of the root entry zone of the fifth, seventh, and ninth cranial nerves can elicit distressing attacks of trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Ephaptic transmission between bare axons and/or central hyperactivity initiated and maintained by the peripheral compression have been suggested mechanisms.’1 The syndrome of the neurovascular as compression of the eighth cranial nerve was first described by Jannetta and later termed "disabling positional vertigo"2,3-a description for a heterogeneous collection of signs and symptoms. We describe 11 patients with brief and frequent attacks of rotational or to-and-fro vertigo for months to years who had prompt responses to carbamazepine. We studied 11 patients (6 women; age range 25-67 years; mean age 51; mean duration of the condition before diagnosis 7-3 years; mean age of manifestation 44-5 years) diagnosed as having vestibular paroxysmia. Only those patients with at least three of the following four features who responded to carbamazepine were diagnosed with vestibular paroxysmia:4,I short attacks of rotational or to-and-fro vertigo (3 patients)

(figure) lasting from seconds to minutes; attacks frequently dependent on particular head position (5 patients); hyperacusis (5 patients) or tinnitus (7 patients) permanently or during the attack; and measurable auditory or vestibular deficits by neurophysiological methods (10 patients). Response to carbamazepine seemed essential since earlier studies on disabling positional vertigo emphasised the ineffectetiveness of vestibular suppressant medications1 without evidence that

antiepileptic drugs (first choice for trigeminal neuralgia) were systematically taken. In audiovestibular testing, 10 of 11 patients exhibited unilateral dysfunction in the symptom-free interval. Carbamazepine was given to all patients orally at an initial dose of 100-200 mg three times daily. All patients responded promptly even to a low initial dose. 8 became symptom-free; 3 reported infrequent residual attacks. The efficacy of treatment

has

been evaluated over 6 years in 1 patient and over 2-3 in 5 others who seem to require a minimum dose of years 200-400 mg per day. One or two wash-out phases were done in 4 patients, all of whom relapsed within 2 days to 2 weeks. The strongest argument for a peripheral nerve origin of the condition in our patients is based on the documented unilateral peripheral audiovestibular deficits in the symptom-free interval in 10 of 11 patients. This is supported by the long duration of monosymptomatic attacks over a mean of 7 years, which makes a central brainstem disorder less likely. None of our patients had an abnormal electroencephalogram, even when an occasional attack occurred during the recording, or multiple sclerosis, which was ruled out by magnetic resonance imaging, analysis of cerebrospinal fluid, and evoked potentials. The dependence of vestibular and auditory symptoms on head position is also indicative of a peripheral disorder. We recommend carbamazepine as first-choice therapy in suspected neurovascular cross-compression of the eighth nerve now

before an operation is

contemplated.

Th Brandt, M Dieterich Department of Neurology, University of Munich, Klinikum Grosshadern, Marchioninistrasse 15, 81377 München, Germany

1 2 3 4

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Møller AR. The cranial nerve vascular compression syndrome, I: a review of treatment. Acta Neurochir 1991; 113: 18-23. Jannetta PJ, Møller MB, Møller AR. Disabling positional vertigo. N Engl J Med 1984; 310: 1700-05. Møller MB, Møller AR, Jannetta PJ, et al. Diagnosis and surgical treatment of disabling positional vertigo. J Neurosurg 1986; 64: 21-28. Brandt Th, Dieterich M. Vertigo in neurovascular cross-compression, vestibular paroxysmia. Nervenarzt 1960; 61: 376-78. Brandt Th. Vertigo: its multisensory syndromes. London: Springer, 1991.

Peripheral lactate and neuronal metabolism

Figure: Anterior (A) and posterior (P), and lateral (right [R], left [L]) postural sway In normal subject (top) and untreated patient with neurovascular cross-compression of the right eighth nerve. Postural sway obtained with force-measuring platform (Kistler, Ostfildern). Patient had slightly increased body sway with eyes closed (bottom

left), which increased during the attack for 26-72 (bottom right), usually in a diagonal AP direction. Direction of preferred body sway changed by 90° if head was turned to R or to L The effects were dependent on head position and combination of auditory symptoms (high-frequency hearing loss, tinnitus at 2000 Hz) with probable involvement of vertical canal and otolith input because of upward spontaneous nystagmus, ocular torsion of both eyes, and tilt of perceived vertical.I.

s

SIR-Maran and colleagues (Jan 1, p 16) demonstrate that a moderate hyperlactataemia attenuates the counter-regulatory response to insulin-induced hypoglycaemia in healthy, nondiabetic volunteers. Subjective awareness of hypoglycaemia and the glucose threshold at which neuropsychological function deteriorated also fell. Maran et al suggest that lactate directly substitutes for glucose as a metabolic substrate for neurons. However, other mechanisms may be operating. The belief that brain relies largely on oxidative metabolism of glucose arose out of the classic observation that fuel uptake by brain from arterial blood could only be demonstrated for glucose and for ketone bodies after fasting. Furthermore, insulin-induced hypoglycaemic coma can be reversed by systemic administration of glucose or mannose (but not lactate). Neurons do indeed have the metabolic apparatus to utilise lactate. Schurr et all demonstrated that neuronal function could be maintained for many hours in in-vitro brain slice preparations by lactate alone. The evidence pointed to direct entry of lactate via pyruvate into the tricarboxylic acid cycle. However, the in vivo significance of such observations depends on blood-brain barrier facilitated transport processes for lactate. Kinetic data suggest that the capacity of the lactate transporter is very much lower than that for glucose. However, there may be situations where BBB permeability to lactate rises and brain lactate uptake becomes significant: for example, there is evidence for this in acutely hypoglycaemic diabetic

dogs.2 Experiments suggest that individual brain regions enter a brief period of non-oxidative, glycolytic metabolism behind the blood-brain barrier upon activation. Transient increases in extracellular lactate are detectable. The subsequent return to normal lactate levels seems to be due to neuronal reuptake and metabolism rather than loss to the blood.3 Astrocyte glycogen 799