Eur Neurol 2001;45:121–122

Transient Ischaemic Attacks and Status
epilepticus in HTLV-1-Negative Adult T-Cell
Leukaemia/Lymphoma
N.J. Gutowski a, D.C. Kinsella b, C.D. Sheldon c, M.A. Pocock d
Departments of a Neurology, b Radiology, c Respiratory
Medicine and d Haematology, Royal Devon and Exeter
Hospital and School of Postgraduate Medicine and Clinical
Sciences, University of Exeter, UK

Adult T-cell leukaemia/lymphomas (ATLL) have an aggressive
course and are linked to human T-cell leukaemia/lymphoma virus-1
(HTLV-1). There is a leukaemic phase in 1 66% often with cutaneous
lesions and hypercalcaemia. ATLL has four subtypes: acute (65%),
lymphoma (25%), smouldering (5%) and chronic (5%) [1]. A case of
HTLV-1-negative ATLL is described. The rare neurological manifes-

tations were transient ischaemic attacks (TIAs) and status epilepticus.
A 37-year-old right-handed man presented with sudden onset
numbness affecting the right side of the face, right arm and leg and an
expressive dysphasia lasting 10 min. Two days later he had numbness of sudden onset in the same distribution lasting 5 min. There
was no weakness or headache. He was a non-smoker who drank alcohol occasionally. After commencing aspirin he had no further events.
Examination was normal.
The past history revealed that 20 months before he had had shortness of breath and cough. Diffuse interstitial shadowing was seen on
chest X-ray. Transbronchial biopsy showed a patchy, dense interstitial infiltrate of mature T lymphocytes. Lymphocytic interstitial
pneumonitis was diagnosed. The following investigations were normal or negative: an infection screen (including HIV-1 and -2),
autoantibodies, immunoglobulins and duodenal biopsy. Lymphadenopathy was absent on chest and abdominal computed tomographic
(CT) scan. The pneumonitis responded to prednisolone which was

Fig. 1. a An axial MRI image (T2-weighted; TR 5,816ms/TE 120 ms), pre-chemotherapy. There is marked increased
signal involving the white matter of both cerebral hemispheres. b Photomicrograph of a centrifuged sample of CSF
showing abnormal T lymphocytes with highly convoluted nuclei (flower cells; scale bar = 10 ÃŒm).

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maintained at low dosage. After commencing prednisolone a mild
peripheral T-lymphocytosis (5.6–6.4 ! 109/l; normal 1.1–3.5 !
109/l) was found. Bone marrow aspirate and trephine were normal.
At neurological presentation, autoantibody, coagulation, thrombophilia, lipid and biochemical screens were normal, except for a
small IgG kappa paraprotein band of 3.9 g/l. The peripheral lymphocytosis was 7.3 ! 109/l. Less mature lymphocytes were seen on blood
film. A T Á gene rearrangement was found. Bone marrow aspirate
showed 30% lymphocytes and an abnormal lymphoid population. A
further infection screen was negative (including HIV-1 and -2 and
HTLV-1 and -2 on two occasions).
Eleven weeks after his TIAs the patient was admitted in status
epilepticus with generalised tonic-clonic seizures having had a gradual onset headache over the previous 4 days. There were no focal
signs. A magnetic resonance (MRI) scan showed diffuse cerebral
white matter signal change, sparing the corpus callosum and brainstem (fig. 1a). There was no meningeal enhancement. Cerebrospinal
fluid (CSF) revealed 1,200 abnormal convoluted T lymphocytes/ÃŒl
(fig. 1b), an elevated protein (3.0 g/l) and a normal glucose. An infection screen was negative, intrathecal JC antibody and DNA were not
detected. Investigations confirmed ATLL confined to the central nervous system (CNS), bone marrow and blood. The patient responded
to phenytoin, phenobarbitone and intrathecal and intravenous methotrexate with folinic acid rescue. He made a complete clinical neurological recovery, but later died of multiple organ failure. A postmortem could not be obtained.
This is an unusual case of HTLV-1-negative lymphoma-type
ATLL [1]. The initial pulmonary infiltration was diagnosed as lymphocytic interstitial pneumonitis. The ATLL subsequently infiltrated the cerebral white matter and leptomeninges, causing the rare
neurological complications of TIAs and status epilepticus. A minority of seronegative HTLV-1 ATLL cases (7–9.5%) have been reported
[2, 3].
The incidence of ATLL CNS involvement varies from 2.5% in
Japan (all HTLV-1-positive) [4] to 21% in Brazil [3], leptomeningeal
infiltration is commonest [5]. Subclinical involvement may be higher
[5]. Most ATLL patients die of systemic disease progression, the
median survival time is 6–7 months [3, 4]. Isolated ATLL CNS
relapses [5] correlate with a higher lymphocytosis, serum lactate
dehydrogenase and calcium levels at diagnosis (not found in the
present case).
TIA has only been described in 1 other case of ATLL, but the
patient was HTLV-1-positive with a progressive neurological deficit
and widespread grey and white matter infiltration [6]. The pathogenesis of TIA may be vascular infiltration as described in intravascular
lymphoma. Status epilepticus as a neurological manifestation of
ATLL has not been described. This may have occurred because of a
sudden onset of leptomeningeal infiltration. Seizure control by anticonvulsants and chemotherapy induced CSF lymphocyte reduction
uniquely allowed clinical neurological recovery despite cerebral
white matter infiltration.

3 Pombo de Oliveira MS, Matutes E, Schulz T, Carvalho SM, Noronha H,
Reaves JD, Loureiro P, Machado C, Catovsky D: T-cell malignancies in
Brazil, clinico-pathological and molecular studies of HTLV-1-positive and
-negative cases. Int J Cancer 1995;60:823–827.
4 Lymphoma Study Group (1984–1987): Major prognostic factors of patients with adult T-cell leukemia-lymphoma: A cooperative study. Leuk
Res 1991;15:81–90.
5 Teshima T, Akashi K, Shibuya T, Taniguchi S, Okamura T, Harada M,
Sumida I, Hanada M, Niho Y: Central nervous system involvement in
adult T-cell leukaemia/lymphoma. Cancer 1990;65:327–332.
6 Taguchi H, Sonobe H, Yamoto K, Takeuchi T, Ookawa K, Kodama H,
Ohtsuki Y, Miyoshi I: Central nervous system involvement of adult T-cell
leukaemia-lymphoma with multinucleated giant cells in the brain, skin and
kidney. Cancer 1993;71:133–137.
N.J. Gutowski, Department of Neurology
Royal Devon and Exeter Hospital
Barrack Road, Exeter EX2 5DW (UK)
Tel. +44 1392 402492, Fax +44 1392 402721

References
1 Matutes E: T-Cell Lymphoproliferative Disorders: Classification, Clinical
and Laboratory Aspects. Amsterdam, Harwood Academic, 1999.
2 Shimoyama M, Kagami Y, Shimotoho K, Miwa M, Minato K, Tobinai K,
Suemasu K, Sugimura T: Adult T-cell leukemia/lymphoma not associated
with human T-cell leukemia virus type 1. Proc Natl Acad Sci USA 1986;83:
4524–4528.

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