No biochemical abnormalities of the blood, urine, or CSF have been detected. The genetics have been mentioned and testing can be used to affirm the diagnosis. Skin biopsy, showing Lafora bodies, may be helpful ion diagnosis, especially if none of the known mutations is detected. The EEG shows diffuse slow waves and spikes as well as bursts of focal or multifocal discharges. Altered hepatocytes with homogeneous PAS-positive bodies that displace the nuclei have been observed in both the presymptomatic and symptomatic stages of the disease. These inclusions have been seen in skin and liver biopsies, even though liver function tests were normal. Neuropathologic examinations have shown a slight loss of granule and Purkinje cells and loss of neurons in the dentate nuclei, inner segment of globus pallidus, and cerebral cortex in addition to the Lafora bodies. The latter may also be seen in the retina, cerebral cortex, myocardium, and striated muscles. Antiepileptic drugs, especially methsuximide and valproic acid, help in the control of the seizures but have no effect on the basic process.
Juvenile Ceroid Lipofuscinosis (Batten Disease,
As stated earlier, this is one of the most variable forms of the lipidoses. The salient clinical features of the later-onset types are severe myoclonus, seizures, and visual loss. In the juvenile type, the first lesions are seen in the maculae; they appear as yellow-gray areas of degeneration and stand in contrast to the cherry-red spot and the encircling white ring of Tay-Sachs disease. At first, the particles of retinal pigment are fine and dust-like; later they aggregate to resemble more the bone-corpuscular shapes of retinitis pigmentosa. The liver and spleen are not enlarged and there are no osseous changes. The usual development of these and other manifestations of the disease were outlined by Sjögren, who studied a large number of the late infantile and juvenile types of cases in Sweden. He divided the illness into stages, the first of which was visual impairment, followed approximately sequentially by generalized seizures and myoclonus, often with irritability, poor control of emotions, and stuttering, jerky speech at 2 years, then gradual intellectual deterioration to which were added cerebellar ataxia and intention tremor, in this respect coming to resemble Wilson disease. Finally, the patient lies curled up in bed, blind and speechless, with strong extensor plantar reflexes, occasionally adopting dystonic postures. Life usually ends in 10 to 15 years.
As mentioned earlier, the genetic underpinnings of this group of lipidoses have been determined for most of the subtypes of neuronal ceroid lipofuscinosis (see Mole and Cotman). These genes have been designated CLN 1 through 9 and they embody over 100 different mutations. Batten disease is caused by CLN3, which codes battenin, a lysosomal transmembrane protein but its function is currently not known.
In the early stages, the EEG pattern of random, high-voltage, triphasic waves is diagnostic; later, as the seizures and myoclonic jerks become less frequent and finally cease, only delta waves remain. The electroretinographic waveforms are lost once the retina is affected. The lateral ventricles are slightly dilated on CT and on MRI. The CSF is normal. Diagnosis can be confirmed by the appearance of inclusions of a curvilinear “fingerprint” pattern in electron microscopic study of biopsy material, particularly of the eccrine sweat glands of the skin.