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Downbeat nystagmus from heat stroke
  1. GREGORY P VAN STAVERN,
  2. VALERIE BIOUSSE,
  3. NANCY J NEWMAN
  1. Department of Ophthalmology, Emory Eye Center, 1365-B Clifton Road, Atlanta, GA 30322, USA
  2. Department of Neurology, Emory University School of Medicine
  3. Department of Neurological Surgery
  1. Dr Nancy J Newman ophtnjn{at}emory.edu
  1. VALERIE BIOUSSE,
  2. JANET C LEINGANG,
  3. NANCY J NEWMAN
  1. Department of Ophthalmology, Emory Eye Center, 1365-B Clifton Road, Atlanta, GA 30322, USA
  2. Department of Neurology, Emory University School of Medicine
  3. Department of Neurological Surgery
  1. Dr Nancy J Newman ophtnjn{at}emory.edu
  1. NANCY J NEWMAN
  1. Department of Ophthalmology, Emory Eye Center, 1365-B Clifton Road, Atlanta, GA 30322, USA
  2. Department of Neurology, Emory University School of Medicine
  3. Department of Neurological Surgery
  1. Dr Nancy J Newman ophtnjn{at}emory.edu

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Downbeat nystagmus is an ocular motility disturbance that may be seen in various pathological conditions.1 Although classically associated with structural lesions of the cervicomedullary junction or cerebellum, it can also occur in the setting of toxic insults and metabolic abnormalities.1 Heat stroke is the most severe form of heat related illness, and is associated with multisystem organ failure. Heat stroke is infrequently associated with a cerebellar syndrome. We describe a case in which downbeat nystagmus was associated with a midline cerebellar syndrome in a patient with heat stroke, suggesting that the vermal cerebellum and vestibulocerebellum may be particularly susceptible to thermal injury.

A previously healthy 22 year old man without relevant medical history collapsed while on a 4 mile run during military basic training. Initial core body temperature was 39ºC. He was incoherent and combative. Laboratory data showed increased creatine kinase, increased liver function tests, and prolonged coagulation variables. Measures to lower body temperature were initiated and he was transferred to our institution.

On arrival, core body temperature was 37ºC. He was somnolent but able to follow commands. His sodium concentration was 135, potassium 3.2, calcium 7.5, magnesium 1.6, alanine transaminase (ALT) 2739, aspartate transaminase (AST) 2112, white blood count 4.2, haemoglobin 12.5, platelet count 43 000, international normalised ratio (INR) 2.9, and ammonia 33. Serological tests for HIV and RPR were negative. An ECG and chest radiograph were unremarkable.

Over the next few days, the patient's liver enzymatic activity improved. He received several transfusions to correct his thrombocytopenia and hypocoagulability. Three days after admission, the patient's family noted that his speech was slurred. The patient complained of blurred vision when reading or looking down.

Neuro-ophthalmological examination 5 days after the onset of his visual symptoms showed near visual acuity of J16 in primary gaze (secondary to oscillopsia) and J1 in upgaze. Kinetic perimetry was full in both eyes. Pupils, external examination, anterior segments, and fundi were within normal limits. Motility examination showed full ductions and versions. Vertical and horizontal saccades were hypometric. Vertical and horizontal smooth pursuit were abnormal (vertical more than horizontal), showing low pursuit gain. There was impaired suppression of the vestibulo-ocular reflex. Downbeat nystagmus was present in primary gaze, worsening in downgaze, and gaze down and laterally. This was poorly suppressed by fixation. His neurological examination showed cerebellar ataxia (truncal more than appendicular), and dysarthria.

A high quality MRI of the brain with and without contrast and with diffusion weighted imaging was performed 6 days after the onset of visual symptoms and was normal. A lumbar puncture showed normal opening pressure and normal CSF contents. Thiamine was added empirically with no effect. Magnesium was corrected to a concentration of 2.6 mg/dl, with no change in the downbeat nystagmus. The patient was discharged to a rehabilitation facility. He was lost to follow up.

Slow upward drifts and downward rapid phases characterise downbeat nystagmus. The velocity and amplitude of the rapid phases are often maximal when looking downward and laterally. Upward gaze typically dampens or eliminates downbeat nystagmus. Several mechanisms responsible for the syndrome have been proposed, including dysfunction of a neural integrator located in the brainstem, tonic imbalance in the vertical semicircular canal and ocular motor pathways, and an imbalance in the otolith-ocular reflex.1 Experimental studies have shown that lesions of the posterior midline cerebellum can produce downbeat nystagmus. Takemori and Suzuki, for example, produced downbeat nystagmus in rhesus monkeys with bilateral floccular lesions.2 Experimental evidence suggests that the flocculus, presumably through Purkinje cell activity, exerts an inhibitory influence on the mechanisms responsible for producing pathological nystagmus.3 Downbeat nystagmus also can be seen with lesions of the cervicomedullary region—such as Chiari malformation or basilar invagination. It may be a manifestation of ischaemic or demyelinating disease in this region or in the cerebellum. It has also been associated with lithium toxicity, B12 and thiamine deficiencies, and hypomagnesaemia.1

Heat stroke is the most severe form of heat related illness. It results from a failure of thermoregulatory mechanisms, causing increase of core body temperature to extreme levels. Predisposing factors for heat stroke include lack of acclimatization, fatigue, obesity, sleep deprivation, and deconditioning. It is characterised clinically by signs and symptoms of CNS injury, core temperature greater than 39ºC (107ºF), and multisystem organ failure.4 Involvement of the CNS in heat stroke may infrequently include cerebellar dysfunction. The cerebellar syndrome associated with heat stroke classically consists of both truncal and appendicular ataxia, horizontal nystagmus, and scanning dysarthria. The clinical characteristics, neuroimaging findings, and neurologic outcomes of cases published since the advent of neuroimaging are summarised in the table. All of the patients had some degree of midline cerebellar dysfunction, and all had initially normal neuroimaging studies.

Cerebellar Purkinje cells are known to be susceptible to metabolic stress, particularly hypoxic-ischaemic injury. There is evidence that the cerebellum in general, and Purkinje cells in particular, are selectively vulnerable to thermal injury. Heat shock proteins are a family of proteins that function in reparative and protective processes essential for cellular survival. Thermal injury has been shown to induce the transcription of heat shock protein in the rabbit cerebellum.12 This may reflect an increased demand for thermal injury repair by Purkinje cells.

Our case is unique in that our patient had a midline cerebellar syndrome with downbeat nystagmus in the setting of heat stroke. Although hypomagnesaemia has been implicated as a cause of downbeat nystagmus, our patient's magnesium concentration was only slightly below normal for our laboratory. Furthermore, the syndrome persisted even after correction of his serum magnesium into the normal range. It may be that in the setting of an already compromised cerebellum, even borderline hypomagnesaemia may promote or accentuate downbeat nystagmus.

Our case provides clinical findings which are compatible with experimental data supporting localisation of downbeat nystagmus to the vestibulocerebellar region. It provides further evidence that this region may be particularly susceptible to thermal injury. The normal diffusion weighted MRI also supports the theory that cerebellar damage in heat stroke is caused by direct thermal injury, rather than a hypoxic-ischaemic insult.

Clinical characteristics of published cases of cerebellar syndrome from heat stroke

Acknowledgments

The work was supported in part by a departmental grant (Ophthalmology) from Research to Prevent Blindness, New York, NY, and a National Institute of Health CORE grant P30-EY0 6360. NJN is a recipient of a Research to Prevent Blindness Lew R Wasserman Merit Award.

References

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