Lenticular Degeneration

LENTICULAR DEGENERATION, a general name for a series of heterogeneous, genotype-determined diseases, united by the predominant localization of the abiotrophic process in the striatal, resp. striopallidal system (nucl. lenticularis). The similarity in localization leads to similarity in clinical syndromes, characterized by the presence of extrapyramidal disorders (hyperkineses or hyperkineses associated with extrapyramidal immobility) without paralysis and sensory disturbances, and in more diffuse processes, intellectual disorders may be added to this picture; the process is often combined with atrophic cirrhosis of the liver ('hepato-lenticular degeneration') or with greenish pigmentation of the peripheral parts of the cornea (so-called 'Kayser-Fleischer ring'). The concept of L. d. includes a number of different diseases, the nosological independence of which is still debated at present. The following three forms are most clearly distinguished among these: 1) Wilson disease (see.), also called 'progressive L. d.'; 2) Westphal-Strümpell disease (see.), at one time called by Westphal 'pseudosclerosis' (the similarity to disseminated sclerosis was meant; this name, incorrect in substance, has however remained to the present time), and 3) torsion spasm of Zielen-Oppenheim, otherwise torsion dystonia, dystonia musculorum deformans, dysbasia lordotica progressiva. The first two forms differ from each other in a number of clinical and anatomical signs, but since all these signs are highly variable, many authors wanted to see in this proof of the identity of both diseases. Wilson disease is characterized by tremor, extrapyramidal rigidity with a tendency to distal contractures, forced laughter, dysarthria, dysphagia, intellectual impairment, cirrhosis of the liver and sometimes enlargement of the spleen. Sporadic cases are not uncommon. Often brothers and sisters of healthy parents become ill. Sometimes cases were observed in the lateral branches of the family (Fig. 1). Figure 1. Family with Wilson disease. The proportions of patients in relation to healthy brothers and sisters approach 1:4; there are thus all grounds to consider Wilson disease an autosomal recessive form (Hall). Westphal's disease differs by a more pronounced and more coarse sweeping hyperkinesia, while the phenomena of extrapyramidal rigidity recede here to the second place; moreover, in this form, the deposition of a special greenish-brown pigment in the skin, meninges, liver and (which is especially important for ante-mortem diagnosis) in the peripheral parts of the cornea is very often observed. Most cases of pseudosclerosis also follow a recessive course of inheritance, although some observations suggest the existence of a dominant variety of this condition. Patho-anatomically, Wilson disease is characterized by significant, macroscopically visible necrotic changes in the striatum [see separate table (Vol. V, pp. 31-32)], while Westphal's pseudosclerosis is characterized by diffuse histological changes in the brain only with a quantitative emphasis in the striatum area. However, soon after the original descriptions, it turned out that cirrhosis of the liver is also observed in Westphal's disease, while the Kayser-Fleischer ring can be found in typical Wilson patients; the pathognomonic significance of these symptoms thus fell away. Similarly, the symptomatic boundary has greatly blurred, as many atypical and transitional cases have been discovered. Genetic study also did not allow to confidently separate both forms, since both of them, at least in their main mass, consist of recessive mutations. Finally, the patho-anatomical difference has largely smoothed out thanks to the work of subsequent researchers, who found in Wilson disease peculiar (so-called Alzheimer's) changes in the glia, characteristic of pseudosclerosis. Thus, the unitary view gradually spread, according to which the Wilson syndrome and the Westphal-Strümpell syndrome represent only accidental variations of hepatolenticular degeneration. However, this contradicts the fact that in some families cases of the Wilson type predominantly appear, while other families are characterized by Westphalian symptomatology. One should therefore think that both these forms, despite far-reaching similarity, are still not identical. This question cannot yet be considered finally resolved. On the contrary, torsion spasm of Zielen-Oppenheim, already after the first descriptions (1908-11), was isolated as an independent disease due to a number of clinical and etiological features inherent in this form. These include: the predominant manifestation of hyperkinesis in the form of powerful torsion convulsions increasing during walking, a slower course, preservation of intelligence, as well as the circumstance that this disease was observed almost exclusively among Jews of Central and Eastern Europe. The combination of torsion dystonia with hepatolenticular degeneration (Oppenheim, Hall and others) was mainly caused by the fact that in two autopsies (Thomalla, Wimmer) typical changes in the liver and brain were found: changes characteristic of Wilson disease in one case, and of pseudosclerosis in the other. However, both these cases should be interpreted as 'symptomatic' torsion spasm, i.e. as Wilson disease, resp. Westphal's disease, in which, due to some, as yet little studied peculiarities of the localization of the process, hyperkinesis took the form of torsion spasm, similar to what is often observed in epidemic encephalitis. Indeed, later autopsy results were published in the so-called genuine torsion dystonia (Schüle; 1923), where there were no changes in the liver, and the histopathology of the brain rather approached that characteristic of Huntington's chorea (cellular degeneration of the striatum). Thus, anatomically, torsion dystonia also proved to have its own characteristics. It enters the collective group of L. d. as a completely independent nosological form. Like other L. d., torsion dystonia is an autosomal recessive form. The sick are mainly children of healthy parents, sometimes cases occur in the lateral branches of the family; sporadic cases are common. In some observations, consanguinity of parents was noted (Fig. 2). Individual minor hyperkineses, not Figure 2. Family with torsion spasm. infrequently noted in healthy relatives (chorea, tics, tremor, etc.), should in this case be regarded as an expression of their heterozygous gene structure. Some families have their own special family variants; thus, in the family represented in the diagram, the disease began with the same deformity of the hands and was complicated by nystagmus and unilateral central paralysis of the facial nerve; conversely, in the family of Mankovsky and Cherny, the process began with the foot; Kehrer observed in three sick sisters (parents-cousins) a combination of torsion dystonia with idiocy and pigmentary retinitis, etc. In individual cases, the disease was transmitted directly from parents to children (Dzerzhinsky). It cannot yet be said whether we are dealing here with a special dominant form of torsion dystonia or whether some other explanation applies: an unusually pronounced manifestation of the heterozygous structure of parents or perhaps cases of symptomatic torsion spasm embedded in a dominant family with Huntington's chorea (Mankovsky, Cherny). The entire group of described forms is by no means yet well studied. Here one still often encounters poorly classifiable cases: various atypical combinations, congenital cases, formes frustes, etc. Also, the nosological boundaries between these forms and some other hereditary diseases of the nervous system with predominant involvement of the extrapyramidal apparatus, such as double athetosis (some consider that torsion dystonia and double athetosis are generally the same disease), progressive extrapyramidal rigidity, some forms of myoclonus, etc., have not yet been clarified. The nosological fragmentation within the large group of L. d. thus cannot yet be considered completed. The far-reaching disagreements on this matter in modern neurological literature are largely explained by the fact that the classification of these forms is mostly attempted on a purely clinical-anatomical basis without taking into account genetic data.