Hans H. Reese

THE TREATMENT OF ACUTE PORPHYRIA WITH CHELATING AGENTS: A REPORT OF 21 CASES

Excerpt Acute porphyria, especially its therapy, has challenged the clinician for years. The mortality rate when associated with severe neuropsychiatric manifestations is quoted as from 80 to 90%.1...

The benign proximal spinal progressive muscular atrophies.

Investigations by W o h l f a r t , F e z & Eliasson (1955), and by Kugelberg & Welander ( 1956) established proximal spinal progressive muscular atrophy as a distinct entity. The group of proximal spinal muscular atrophies (henceforth referred to as the WK\V (Wohlfart, Kugelberg, Welander) syndrome) now includes forms with both early and late onset, the latter cases without ( Wiesendanger 1960) and with bulbar syniptoms (Magee & DeJong 1960, Myrianthopoulos & B r o w n 1954, Tsukagoshi et al. 1965, Tsukagoshi e t al. 1966). Original reports of the early onset WI<W syndrome suggested probable autosomal recessive inheritance ( W o h l f a r t et al. 1955), but reports of late onset type of the WKW syndrome indicated an autosomal dominant mode of inheritance ( A r m s t r o n g e t al. 1966, Magee & DeJong 1960) with incomplete expression in certain families. The first reports described onset in early childhood or adolescence, hyporeflexialike weakness and atrophy predominantly of the proximal muscles, distinct fasciculations and slow progression over many years. The syndrome has often been mistaken for muscular dystrophy. Even W o h l f a r t (1942) reported a case of muscular dystrophy with fibrillary twitchings which we now know belongs to the WKW syndrome. Others have postulated a relationship between the WKW syndrome and amyotonia congenita. On purely clinical grounds amyotonias are divided into a malignant

Therapy of acute, chronic and mixed hepatic porphyria patients with chelating agents.

THE EFFECTIVENESS of the chelating agents 2,3-dimercaptopropanol ( BAL) and ethylenediamine tetraacetic acid (EDTA) in the therapy of acute, chronic, and mixed porphyria patients with severe neuropsychiatric symptoms has been reported in 15 of 20 patients treated with these agents.’-3 Individual cases have been cited4v6 in which BAL therapy seemed effective in arresting advancing symptoms of acute porphyria. Schrumpfs reported that a case of chronic porphyria with cutaneous symptoms benefited under BAL therapy. Paul and ThyressonT reported that a case of chronic porphyria improved with BAL therapy, while Dean* treated an acute porphyric patient with BAL for one day and felt it was ineffective. Kehoe, Rudensky, and Reynolds9 likewise treated one of two acute porphyric twins with low dosage of BAL for ten days but felt it was ineffective, although subsequently the patient went on to recovery from neurologic and psychiatric symptoms without other medical therapy during hospitalization. A mixed porphyric with porphobilinogenuria (included in a previous series) was reported in detail by Woods, Peters, and Johnsonlo to illustrate the favorable influence of EDTA administered initially by the intravenous route, followed by maintenance on oral EDTA therapy, resulting in continued recovery and protection from cutaneous symptoms. This report is to re-emphasize the effectiveness of chelation therapy in hepatic porphyria. Evidence will be presented to indicate the apparent existence of a porphyric-schizophrenic syndrome; another group of patients, who were clinically acute porphyrics but excreted porphobilinogen rarely, will be designated the “paraporphyric” group. It would appear that the chronic and mixed porphyric consistently excreted urinary copper in excess, while the acute porphyric often showed zinc diuresis before and during chelation treatment. Finally, an alteration of tryptophan metabolism was seen in the acute, chronic, and mixed hepatic porphyric, the porphyric-schizophrenic, and the “paraporphyric” patient. Watson11 divides porphyria into two major forms: first, the porphyria erythropoietica, in which the metabolic error resides in the bone marrow with onset in infancy of mutilating photosensitive dermatitis, and second, the hepatic porphyrias which he subdivides into acute, cutanea tarda, mixed, and latent forms. Acute hepatic porphyria, inherited as a mendelian dominant, is characterized by recurrent gastrointestinal, psychiatric, and neurologic symptomatology occurring singly or in combination. Whereas erythropoietic porphyria is rare, we are of the opinion that hepatic porphyria is much more common than suspected. Hepatic cutania tarda porphyria is manifested by the late onset of photosensitive cutaneous lesions. Hepatic mixed porphyria incorporates a combination of the cutaneous and acute varieties in which cutaneous, neurologic, psychiatric, and abdominal symptomatology appear in varying combinations. Latent forms of the disease exist. Increased delta-amino levulinic acid in the urine in acute porphyrics, as reported by Granick and Vanden Schrieck’z and by Mauzerall and Granick,13 stimulated us to utilize the quantitative determination of delta-amino levulinic acid, a porphobilinogen precursor, as a useful screening device. Eleva-

Myopathy in mice experimentally infected with Schistosoma mansoni

Abstract All mice infected with S. mansoni developed the disease. After 12 weeks of infection, the eggs of the parasite were always found in the diaphragm, usually in a nestlike lesion, and were found with less frequency in the sacrospinalis muscle, usually in a scattered pattern. Our findings are in direct contrast to the previous implications that schistosomes spare the skeletal muscles.

EXPERIMENTAL ANTIMONY TOXICITY ON LOWER MOTOR NEURONS AND MUSCLES OF MICE.

Abstract The occurrence of muscular weakness and wasting in patients with schistosomal infections treated with tartar emetic prompted this investigation of the role of antimony (potassium tartrate) on the lower motor neurons and muscle of mice (lumbar cord, sciatic nerve, myoneural junction, and gastrocnemius). Motor weakness could be demonstrated in the animals and could be correlated with the dosage by testing muscle endurance in an activity cage. The pathological changes in the anterior horn cells are vacuolar degeneration, chromatolysis, satellitosis, and swelling of the nuclei. The edematous sciatic nerves have hydropic degeneration with vacuolation, and fragmentation of axons. The myoneural junctions show swollen ramifications of the axis cylinder and an increase in the number of end-plate nuclei. Some muscle fibers (gastrocnemius) have hyaline and granular alterations with vesicular nuclei, and other atrophic fibers with pyknotic nuclei, but the main changes are in the anterior horn cells, sciatic nerves, and myoneural junction.

A previously unreported myopathy in patients with schistosomiasis

THE CLINICAL OBSERVATION that patients with Schistosoma mansoni, Schistosoma haematobiurn, or both, present with wasting in the form of either localized or diffuse muscular atrophy and weakness of the skeletal muscles, stimulated us to investigate the causes of these clinical findings. The muscular impairment is present in patients who also have clinical cirrhosis as well as in those in whom evidence of hepatic deficiency could not be established. We have restricted this study to the clinical symptoms and signs, to certain biochemical investigations, and to muscle biopsies. The aim of this report is not only to elaborate on the clinical findings in our patients but especially to ascertain probable causes of the muscle pathology. Fifteen schistosomiasis patients ranging in ages from 12 to 40 years (2 females and 13 males) were chosen from the neurological service of the University of Alexandria (table 1 ) . They were submitted to a clinical study with special emphasis on the functions and strength of the muscles, the peripheral nerves, and the nervous system. Patients with a suggestive familial history of myopathy or neuropathy were excluded. Our diagnostic criteria are based on a careful family and personal history, the clinical examination with laboratory data, and in most instances a recovery of ova from feces or urine. The muscle biopsies taken from the gastrocnemius were put in 10% Formalin, then embedded and stained. Thirteen of the 15 patients examined have or have had S . mansoni infection, six having active S . mansoni symptoms with ova being recovered from the feces and seven patients giving a history of S. mansoni infection only. Nine patients have or have had S. haematobium infection, with 3 presenting an active infection with ova in the urine; 6 gave a history of infection only. One patient (No. 13) had an acute-subacute double infection, excreting ova of both species. Six patients gave either a history of the double infection or of an active infection of one and a history of the other. All patients have received antimony therapy. Eleven patients have generalized wasting with weakness of the skeletal muscles, especially noticeable in the lower extremities (Fig. 1) . Of these 11, 8 also have cirrhosis of the liver, while 4 are without cirrhosis. Four of the 15 patients have localized wasting and weakness mainly of the shoulder-pelvic type (Fig. 2) . None of these had cirrhosis. The thymol turbidity, alkaline phosphatase, plasma proteins, and icterus index are within a normal range even in our patients with cirrhosis. Out of this group of 15 patients with muscular abnormality, we have selected for detailed study and presentation one of the localized type (case 14) and another of the much more generalized form (case 5).

Skin lesions and central nervous system diseases.

The recognition of skin lesions is very important and at once projects the physicians diagnostic interest from an apparent surface disability into a much more profound, complex and continuously progressing hopeless illness. In most instances colored illustrations have documented the correlated skin and central nervous system involvement as described here.