Article Text

A new case of late onset Lafora’s disease without generalised seizures
  1. A FERNANDEZ-BARREIRO,
  2. J SICILIA GUILLEN,
  3. P CASTEJON VERA,
  4. J MARTIN FERNANDEZ,
  5. J B ESCRIBANO SORIANO,
  6. M C ANTUNEZ,
  7. R VILLAVERDE
  1. Servicio de Neurologia
  2. Servicio de Anatomia Patologica , Neuropatologia, Hospital Universitario Virgen de La Arrixaca, El Palmar Murcia, Spain
  1. Dr A Fernandez-Barreiro, Servicio de Neurologia Hospital Universitario Virgen de La Arrixaca, El Palmar, Murcia, Spain.
  1. J SOLA PEREZ
  1. Servicio de Neurologia
  2. Servicio de Anatomia Patologica , Neuropatologia, Hospital Universitario Virgen de La Arrixaca, El Palmar Murcia, Spain
  1. Dr A Fernandez-Barreiro, Servicio de Neurologia Hospital Universitario Virgen de La Arrixaca, El Palmar, Murcia, Spain.

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Lafora’s disease is clinically characterised by the triad of epilepsy, progressive dementia, and myoclonus as well as Lafora bodies in the brain and other tissues.

The onset of this autosomic recessive disease is usually between the ages of 6 and 20 with a duration of 2–10 years. It can begin with generalised tonic-clonic seizures or focal seizures which are especially visual. Slight erratic myoclonus appears progressively with twitching movements of the fingers and facial muscles. The EEG records show a slowing of background activity and bursts of spike and wave which are generalised, multifocal, and often sensitive to intermittent luminous stimulation. The disease provokes progressive deterioration leading to cortical and subcortical dementia and eventual death.

Light microscopy of biopsy of the frontal cortex. There are characteristic intraneuronal inclusion bodies of different morphological forms with Nissl granules. Periodic acid Schiff; originally×1000.

The cases in the literature to date, including the families which we studied, all possessed these clinical criteria.1 2

The aim of this letter is to highlight one of our latest cases of late onset Lafora’s disease, which occurred when the patient was 25 years old and who, although not showing evidence of either tonic-clonic or focal seizures, did, however, have dementia and erratic myoclonus over a long period. Blood taken from this patient served in the identification of the Lafora chromosome map.3

The patient was a 40 year old woman who, at 25, after giving birth to a healthy baby girl, began to show symptoms of depression and notions of persecution allied to paranoid psychosis.

At the age of 28 she came into our care with a dystonic reaction to neuroleptic treatment which affected the mouth, neck, and trunk but which cleared up when treatment was suspended. Her family informed us that the patient’s condition had not improved over the previous 2 years and in addition to having memory loss she had become unable to perform normal household tasks.

The patient showed general disinterest and irritability, she was poorly oriented regarding time and space, but was, however, capable of reading, writing, and making small calculations; on the other hand she was unable to interpret a newspaper correctly or remember four consecutive words or digits. In addition, she had dysarthria and pronounced the final words of a sentence in a musical tone. She also had slight myoclonus in her hands and face. Occasionally, after a sudden stimulus she displayed myoclonic jerks in her four limbs but at no time did she lose consciousness. Generalised hypereflexia with negative Babinsky’s sign was seen. The fundus of the eye was normal.

General analysis, routine laboratory analysis, serological tests, and CSF examinations were either normal or negative, as was an EMG study. The visual, auditory, and somatosensory evoked potentials were all normal. Brain CT and MRI all showed evidence of a slight degree of subcortical atrophy.

The first EEG record, carried out the day after admission, showed slightly slow background activity with bursts of slow waves and paroxysms of spikes and waves. Intermittent photic stimulation induced generalised discharges of slow and sharp waves with bursts of spike and polyspike wave complexes in occipital regions. Unexpectedly, on one occasion a massive generalised myoclonic seizure with a frequency of 15 flashes/second was seen but the patient did not lose consciousness. Six subsequent records were carried out with intervals of 4 days but there was no more evidence of photoparoxysmal discharges.

Background activity continued to be slow but there were persistent discharges of slow spike wave complexes of one cycle/second and 100–200 μV in the occipital regions.

Treatment with valproic acid and clonazepam was initiated and the patient was discharged for observation and follow up.

At the age of 29 the patient moved to her parents’ home as she had become unable to carry out any housework or other household tasks, including the care of her child. A Benton and Endo test was done which showed temporal disorientation, short term memory loss, digital agnosia, ideomotor apraxia, and difficulty with reading and writing, expressive language, and logical argument .The patient could not distinguish right from left. The EEG record showed background theta activity as well as slow and sharp waves with a paroxysmal tendency. Intermittent photic stimulation did not induce further paroxysmal discharges.

During subsequent years the patient deteriorated mentally without any major epileptic seizure and only slight myoclonus. Use of valproic acid and clonazepam was suspended.

An axillary biopsy of sweat glands ruled out the presence of Lafora inclusion bodies, although a right frontal cerebral biopsy did show their presence (figure).

The patient is currently 40 years old and has obvious dementia. She moves from bed to armchair in a position of tetraparesis of limbs with pseudobulbar signs, she displays generalised rigidity with cogwheeling phenomenon and amimia, her deep reflexes are brisk, she has only slight erratic myoclonus but no other seizures. The EEG register is slow in background activity and presents multifocal paroxystic discharges of spike and spike waves.

In the literature about Lafora’s disease, there have been few reported cases with late onset.4-6

The peculiarity of our patient is that after having given birth to a child at the age of 25 she was shown to have the disease in a late onset form.

Initially she had psychiatric disturbances leading to progressive dementia with myoclonus. The patient at no point had generalised tonic-clonic or focal seizures.

Treatment with valproic acid and clonazepam was initiated as a precaution, but as the illness progressed and the patient deteriorated and still no major attacks happened, use of both was suspended. The EEGs recorded during evolution were typical with generalised paroxysmal discharges and focal or multifocal and slow background activity. The only clinical seizure that the patient presented was provoked shortly after admission and consisted of massive myoclonus with no loss of consciousness. This was caused by photostimulation in the EEG laboratory. What interested us about the patient’s evolution was the evidence of dementia rather than epilepsy.

An axillary biopsy proved negative, but the cerebral cortex showed inclusion bodies characteristic of Lafora’s disease, most of which were intraneuronal.

Despite the late onset of the illness in this case, studies of blood samples from the patient showed the chromosomal map of Lafora illness.

A patient with dementia and Lafora inclusion bodies but without epilepsy has only previously been described by Suzukiet al.7 This was a patient aged 59 with dementia who showed the histological findings typical of the illness. Our patient, who has now had the disease for 15 years, continues to have dementia and shows no evidence of tonic-clonic or focal seizures. Only slight myoclonus is present

We think that Lafora’s disease could be more common than previously thought and other forms of the illness should be sought, such as late onset dementia without epilepsy, accompanied or not by slight myoclonus. We also think that an axillary cerebral or other tissue biopsy, or a genetic study can show different clinical forms of the disease.

Acknowledgments

We are grateful to Professor Barry Noonan for help in revising the text.

References

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