Introduction
An episode of abrupt, uncontrollable muscle jerking or twitching that can affect the whole body or just a portion of it is known as myoclonus. Myoclonus can happen when a patient is at rest, and motion, excitement, or flashing lights can exacerbate it. Myoclonus frequently occurs continuously and affects the entire body in the final stages of Lafora progressive myoclonus epilepsy.
People with Lafora progressive myoclonus epilepsy frequently have a variety of seizures. The entire body is affected by generalized tonic-clonic seizures, which result in tight muscles, convulsions, and loss of consciousness. Occipital seizures, which can result in temporary blindness and visual hallucinations, are another possibility for those affected. The seizures get worse with time and are harder to cure. Status epilepticus, a potentially fatal seizure disorder, may also appear. Status epilepticus is a prolonged period of unbroken seizure activity that lasts more than a few minutes.
First identified in 1911, Lafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy (PME). It is especially prevalent in Mediterranean nations and some southern Indian regions with high consanguinity rates. Nonetheless, it can occur in any group and is more common, as would be expected, among families.
LD typically begins in adolescence in otherwise neurologically healthy people and is characterized by tonic-clonic, absence, atonic, and visual seizures as well as action and stimulus-sensitive myoclonus. Also frequent are neuropsychiatric symptoms such as apathy, sadness, and behavioral abnormalities.
Following the onset of symptoms, cerebellar ataxia, dysarthria, mutism, fast progressive dementia, refractory status epilepticus, psychosis, and respiratory failure all contribute to death within ten years.
What Are the Causes of Lafora Body Disease?
The laforin dual specificity phosphatase and Malin ubiquitin E3 ligase, which are both involved in a complicated and still largely unrecognized process controlling glycogen metabolism, are the two genes responsible for LD. In a single family, a mutation in the PRDM8 gene has been documented to generate a form of early childhood onset phenotype. LD exhibits specific pathophysiology. Polyglucosans, which are deformed and insoluble glycogen molecules that differ from normal glycogen because they lack the symmetric branching that makes glycogen soluble, are seen in dense accumulations in cells of diverse sorts. The majority of neurons and all regions of the brain contain these polyglucosan accumulations, known as Lafora bodies (LBs).
What Are the Clinical Features of Lafora Body Disease?
The onset of LD symptoms usually occurs in late childhood or adolescence. Early indications of focal visual seizures typically include simple or complicated visual hallucinations and transitory blindness. Myoclonus and other generalized seizure types start soon after, such as tonic-clonic, absence, or drop episodes.
The latter usually occurs at rest and rises in response to emotion, movement, or photic stimulus. The illness frequently manifests as a sneaky near-simultaneous occurrence, or closely successive, of headaches, academic difficulties, myoclonic jerks, generalized seizures, and visual hallucinations.
It is noteworthy that not all visual hallucinations in Lafora patients are epileptic, as some of them initially respond to antipsychotic drugs rather than antiepileptic ones.
How Is the Diagnosis of Lafora Body Disease Done?
Clinical symptoms frequently precede electroencephalogram (EEG) abnormalities, which initially consist of background activity that is practically normal or slowed and localized or generalized paroxysmal activity that is typically not increased by sleep. In particular, the occipital discharges on EEG, which result from a slower posterior dominant rhythm, are strongly symptomatic of the illness in the appropriate clinical situation.
Within a few years, diffuse epileptic discharges frequently occur in superimposed bursts along with a slowdown of background activity. Furthermore, myoclonus, positive or negative, and strong photosensitivity are notable characteristics. Initially, brain MRI scans are typically unremarkable. Fluorodeoxyglucose positron emission tomography identified posterior hypometabolism early in the course of the disease in two of the reported cases.
Giant evoked potentials and improper integration of cortical hyperexcitability can be found through electrophysiological tests. Visual evoked potentials may exhibit longer latencies or no response at all. Further results from TMS point to a complex circuitry malfunction that may involve excitatory and inhibitory systems.
A skin biopsy reveals the myoepithelial cells of the secretory acini of the apocrine sweat glands and the eccrine and apocrine sweat duct cells to have the distinctive periodic acid-Schiff (PAS)-positive glycogen-like intracellular inclusion bodies.
The existence of fibrillary accumulations, typical of polyglucosans, is confirmed by electron microscopy. This diagnostic method is low-invasive and highly sensitive. However, interpreting the biopsy requires skill in separating LB from the typical polysaccharide contents of apocrine sweat glands; otherwise, false-positive diagnoses are frequently made.
What Is the Prognosis of Lafora Body Disease Done?
The prognosis of LD is generally catastrophic and progressive, with mortality occurring 5–10 years following the onset of clinical symptoms. Patients with EPM2A and EPM2B mutations do not significantly differ based on genotype-phenotype correlations. Still, some specific EPM2B mutations seem to be associated with late-onset and slow progression of LD. The best available medications for LD currently have modest success in symptom regulation; hence palliative care is still the mainstay of care. In the early stages of the disease, myoclonus symptoms may be alleviated by commonly used antiepileptic medication.
What Is the Management of Lafora Body Disease Done?
There is little doubt that the health systems of different nations differ significantly, especially between industrialized and underdeveloped cultures. Moreover, health coverage is unique in many industrialized nations, so some patients may benefit from a wide selection of options while others do not. It is also evident that people with LD should receive the most assistance feasible from the current healthcare system. Although LD is an uncommon disorder that cannot be categorized as a public health issue, it significantly affects patients and carers, and society should unite and offer all possible assistance.
No specific antimyoclonic drugs are effective against LD to stop seizures and myoclonus, and the effect lasts the entire duration of the illness. Sadly, they only have a minor impact and have little bearing on how cognitive and behavioral symptoms develop. Patients usually get an AED, commonly valproic acid, after the first generalized tonic-clonic seizure (GTCS).
This typically works well in temporarily suppressing the majority of GTCS, photic sensitivity symptoms, and some myoclonus. Despite the apparent clinical remission, the EEG reveals two peculiar effects that should prompt an early diagnosis of LD: first, the patients experience negative myoclonus, which becomes more noticeable before the more typical myoclonic jerks, and second, the EEG reveals rapidly increasing, permanent interictal changes, including focal occipital spikes.
Conclusion
The current possibilities for patients with lafora disease involve a sensible, successful approach to diagnosis and the rational use of all available instruments to support the patients and their families. As practical, pathogenetically focused medicines are made accessible, we anticipate seeing a significant shift in how LD patients are managed soon.
