Journal of Neurology, Neurosurgery, and Psychiatry 1985;48: 1015-1020

Neuropathy and myopathy in two patients withanorexia and bulimia nervosa

R ALLOWAY, EH REYNOLDS, E SPARGO, GFM RUSSELL

From the Maudsley Hospital, King's College Hospital and the Institute ofPsychiatry, Denmark Hill, London,UK

SUMMARY Two adolescent patients with eating disorders and severe weight loss presented withneuromyopathy. The first was female and had a twenty months' history of bulimia nervosa withweight loss and episodic gorging and vomiting. The second was male with a two-year history ofanorexia nervosa characterised by vegetarianism and increasing food restriction. Both had severewasting and asymmetrical weakness of proximal limb muscles. The first patient deteriorated onrefeeding and became temporarily paralysed. Both had a purpuric rash and haematologicalabnormalities. They made a complete recovery on a mixed diet: vitamin supplements were givento the first but not to the second patient.

Anorexia nervosa is a condition characterised by thefollowing phenomena: a morbid attitude to weightand body size, severe weight loss and amenorrhoeain the female or loss of sexual interest and potencyin the male. Bulimia nervosa, another category ofeating disorder, shares some of the features ofanorexia nervosa. In addition, the patient experi-ences episodic gorging of food and seeks to coun-teract any effect on weight by self-induced vomitingor laxative abuse or both.' Paradoxically, these con-ditions are associated with abundant activity; evenwhen emaciated, patients may frequently continuenormal activities and indeed take extra exercise.This phenomenon has been known for manyyears.23 In the later stages general fatigue is com-mon: more rarely muscle weakness, due tohypokalaemia, occurs. It is at this stage that patientsadmit concern about their health. (For generalreview, see ref 4).We report two adolescent patients, a bulimic girl

and an anorexic lad, both severely underweight, inwhom severe wasting and proximal muscular weak-ness were associated with haematological dysfunc-tion and a diffuse purpuric skin rash. The proximalmuscular weakness progressed to temporary para-lysis in the bulimic girl. The similarity in presenta-

Address for reprint requests: Professor GFM Russell, Departmentof Psychiatry, Institute of Psychiatry, De Crespigny Park, DenmarkHill, London SE5 8AF, UK.

Received 4 August 1984 and in revised form 5 February 1985.Accepted 9 February 1985

tion of both patients and the differences in theirearly response to treatment are discussed in relationto their method of inducing weight loss.

Case 1:A 17-year-old girl presented 20 months after the onset ofweight loss. Prior to her illness she had weighed 65 kg. Shehad intended to follow a weight reducing diet but later thisalternated with uncontrollable gorging and vomiting. Twoweeks before her admission to a general hospital, she hadnoticed weakness and difficulty in climbing stairs at school;moreover, she had become too weak to vomit.On the first admission to the general hospital (fig 1) she

weighed only 36 kg and had lost a further 3 kg before beingtransferred to the Maudsley Hospital. There the patientwas found to be grossly emaciated (fig 2) with a dry skincoloured by a diffuse purpuric rash (fig 3) covering hertrunk, back and upper thighs. Her parotid glands wereenlarged. She was tachypnoeic at rest but otherwise herrespiratory system was normal. Her pulse was 80/min andthe blood pressure 90/60 mm Hg. Lanugo hair covered herback and arms. She had two ischaemic ulcers on her rightforearm and left foot. Neurological examination revealedsevere muscle wasting and weakness of the proximal limbgirdles. She was unable to flex her neck, raise her handsabove her shoulders, stand from a sitting position or sit upfrom a lying position unaided. Once standing, she couldwalk with an unsteady gait. Distal limb power from thewrists and ankles was normal. There was no ocular, facial,pharyngeal or tongue weakness. All arm and knee reflexeswere diminished: ankle jerks were absent and plantarresponses were flexor. Sensory examination, including vib-ration sense at the ankles, was normal. Initial haematologi-cal tests showed a normal haemoglobin level and bloodcount except that the platelets were low at 107 x 103/mm3.

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Fig 1 Graphical representation ofthe sequence ofchangesin body weight, muscular weakness, skin rash andhaemoglobin with calorie intake in the bulimic girl(patient 1). (*measure ofseverity from physicalexamination. Hb Haemoglobin. <Hl> Admission to firstgeneral hospital; <H2> Admission to second generalhospital.)

Plasma creatine kinase was 638 iu/l. The prothrombin timewas normal, as was liver function apart from mild hyper-bilirubinaemia (23 mmol/l). The following plasma levelswere normal: urea, electrolytes, calcium, T.4 and T.3.Serum Vitamin B, was normal and folic acid was 2-8 mg/l.An electrocardiogram and chest radiograph were normal.Further investigations showed a negative Paul Bunnelltest; blood cultures, electron microscopy of stool for vir-uses and antibody titres did not identify a pathogen. Serumlevels of Vitamin E and magnesium were normal. Serumiron was 26 ,Lmol/l and iron binding capacity (IBC) 32,umol/l. Urinary and faecal porphyrins were not abnormal.On the day of admission to the Maudsley Hospital (Day

0, fig 1) the patient was commenced on a 1,500 calorie dietwhich was increased to 3,000 calories on Day 7. On Day 4she was started on daily high potency vitamin B and Cinjections (Parentrovite) with oral folic acid (10 mg mane)and vitamin E (20 mg three times a day). From Day 10 allvitamins were given orally (Vitamin B and C as Multivite)with, in addition, calciferol 6,000 units daily.On Day 3 her physical condition started to deteriorate.

Pitting oedema developed rapidly up to her waist and shegained 12 kg over the next 10 days. Urine output fell toless than 600 ml/day from Day 7 to Day 11. The rashspread and muscle weakness progressed to paralysis of thelower limbs, requiring two-hourly turning in bed. Liverfunction deteriorated: alkaline phosphatase rose to 201iu/l, aspartate transaminase to 151 iu/l and glutamyl trans-peptidase to 37 iu/l with total serum protein falling to 50 g/l(albumen 30 g/l). On Day 4 the platelet count was un-

Fig 2 Full-length photograph of the bulimic girl

(patient 1) on Day 2 ofadmission showing the severe

muscle wasting and distribution of the skin rash.

Alloway, Reynolds, Spargo, Russell

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Neuropathy and myopathy in two patients with anorexia and bulimia nervosa

Fig 3 The anterior truncal view to show more detail ofthe

purpuric skin rash.

recordable. Plasma electrolytes including potassiumremained normal throughout the course of the illness.

From Day 14 the patient's physical state improved: mus-

cle power and reflexes improved steadily and were almost

normal one month later. This was accompanied by a

gradual reduction in creatine kinase which was normal by

Day 19. By Day 21 her rash had gone. A spontaneous

diuresis occuffed on Day 14 corresponding to the sharploss in weight shown in fig 1. On that day the haemoglobinlevel reached a minimum of 8*4 g/dl but it slowly rose

thereafter while a reticulocytosis continued for 2 months.

Over this time course liver function returned to normal.

The patient was discharged after 4 months, weighing54 kg.Three electrophysiological studies were performed dur-

ing the admission. The first electromyogram (EMG) was

on Day 7, at the height of the patient's weakness. Deltoid,biceps brachii, vastus medialis and first dorsal interosseouswere sampled. Myopathic changes in the proximal muscleswere shown by an increased incidence of polyphasic poten-tials, mainly stable but with occasional increase in jitter.Interference patterns were dense and of normal amplitude.Neuropathic changes were found from nerve conductionstudies (see table): the sural sensory action potential(SAP) was barely detectable; radial (24 AV), median (14,uV) and ulnar (12 ,V) SAPs were within the statisticalrange of normal but considerably smaller than would nor-

mally be recorded in a girl of this age and build. The mixednerve potential recorded over the ulnar nerve trunk in thecubital sulcus (22 jAV) was reduced by any criteria. On thesecond examination on Day 21 deltoid and rectus femorisshowed minor myopathic changes, the sural nerve SAP wasnow 7 pV (normal minimum 10 IAV) and the other poten-tials larger than before (35 ,AV, 35 ,uV, 20 ,tV, 35 ,uV). Atthe third examination 3 months later, when power andreflexes were normal, minimal myopathic change was stilldetectable in the deltoid, and nerve conduction was normal(sural SAP 20 ,uV).

Case 2:A 16-year-old lad was admitted 2 years after he hadbecome vegetarian and slowly restricted his food intake.For the last 4 months, weight loss had accelerated and forone week he had been too weak to get out of bed.On admission he weighed 40-8 kg: an estimated healthy

weight was 67 kg. His skin was covered in a purpuric rashwhich he had noticed 2 weeks before. He had moderateproximal muscle weakness involving all four limbs andtrunk. He had difficulty in maintaining his arms raised andwas unable to stand up from a kneeling position. Distalpower was normal. Biceps, triceps supinator and kneereflexes were diminished: both ankle jerks were normaland plantar responses were flexor. Sensation was normal.Haematological tests showed low platelets 123 x 103/mm3and a slight reduction in serum iron and IBC. Plasmacreatine kinase was 43 iuVl. The following plasma levelswere normal: urea, electrolytes (including potassium), cal-cium, vitamin B12 and glucose: thyroid and liver functiontests were normal. Red cell transketolase was 39 iu/l (nor-mal range 35-90 iu/l) on the fifth day after admission butby then the patient had begun to accept food so that anyabnormality might have been corrected.

Table Nerve conduction measurements in both patients performed on given days after admission, and in normals

Action potential: Normal Patient I Patient 2Sensory (SAP), Mixed nerve (MNAP) values Day 10

Day 7 Day 21

Left sural SAP >10 IsV barely 7 ,uV 6 I,V>40 rn/s detectable 50 m/s -

Right radial SAP >30 AV 24 ,uV 35 ILV 43 AVRight median SAP >20 AV 14 AV 35 AV -

Right ulnar SAP >15jV 12KuV 20 ,uVRight ulnar MNAP >30 AV 22 AV 35 tV -

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On admission the patient received a 1,000 calorie diet.This was continued for three weeks and was then increasedto 3,000 calories daily. Weight gain was steady between1-2 kg per week without the pronounced oedema whichhad occurred in Case 1. His rash disappeared over the nextfour weeks and his muscle power steadily improved andwas normal, with normal reflexes, within eight weeks. ByDay 7 his platelet count was normal. His haemoglobin hadfallen to 10-7 g/dl at the end of the third week and his whitecell count was 3,700imm3. Both were normal by the end ofthe fourth week. Creatine kinase remained normal. He wasdischarged after four months at a weight of 62 kg.The investigations of the neuromuscular disorder

included an EMG, the measurement of sensory actionpotentials and a muscle biopsy. The EMG in Week 2, at atime of moderate clinical improvement, showed somemyopathic changes. Thus, there was an increase in theincidence of notched motor unit potentials, and on lowfrequency attenuation a mild, stable increase in thenumber of components, spread over a slightly increasedduration. Slight neuropathic changes were shown by areduced sural nerve SAP (6 ,uV), but the radial SAP wasnormal (43 AV) (See table). Both were of normal form andlatency.The muscle biopsy was performed in Week 6: this was

taken from the left quadriceps muscle when the patientweighed 50 kg. Figure 4 shows a section of the quadricepsmuscle with atrophy of both type I and type II fibres,although this was more pronounced in type II fibres, virtu-ally all of which were atrophic. There was no evidence ofnecrosis, inflammatory infiltrate or loss of fibres. Figure 5represents the distribution of fibre size for each type ofmuscle fibre obtained from the biopsy sample. The major-ity of type II fibres have diameters less than the range(40-80,m) seen in normal adult muscle, confirming aselective type II atrophy. Quantitative morphometric

Fig 4 Cryostat section ofleft quadriceps muscle showingselective atrophy oftype 1I fibres (dark). Myosin adenosinetriphosphatase (A TPase) at pH 9-4 x 150.

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i1o 140Fig 5 Distribution curves offibre size in muscle biopsy inpatient 2. Type I fibres 0.....0. Type 1 fibres ) O0.The majority oftype 11 fibres have diameters less than therange (40-80 u) seen in normal adult muscle.

analysis showed normal proportions of fibre type (Type I38%; Type II 62%). It also confirmed severe type II atro-phy (mean diameter 35-1 ,um + 11-0, compared with anormal value of 65 ,um,5 and a slight atrophy of type Ifibres (mean diameter 54-0 ,um + 11-7, compared with thenormal of 61 ,um).

Discussion

Muscular weakness is not recognised as occurring inanorexic or bulimic patients unless hypokalaemiasupervenes. Sletteb0 et a16 recently described wast-ing of skeletal muscles and reduction in size of mus-cle fibres from biopsy material in patients withanorexia nervosa, but none of them had a paresis onclinical examination. The complications found in thetwo patients described here have not hitherto beenreported. Yet it is almost certain that they were theresult of malnutrition.The organ systems involved in both patients were

neuromuscular, haemopoeitic and cutaneous. In thefirst patient who had bulimia nervosa the liver, car-diovascular and renal systems became involved afterrefeeding. Distinctive deterioration in her physicalcondition was an important difference between thetwo patients, in an otherwise very similar initial pre-sentation. It is useful to discuss previous findings inpatients with anorexia nervosa and other nutritionaldisorders, to see whether light can be shed on themechanism underlying the clinical state.The neuromuscular abnormalities in our two

patients were those of a peripheral neuropathy andmyopathy. Clinically the myopathy dominated. Evi-

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Neuropathy and myopathy in two patients with anorexia and bulimia nervosa

dence of it included proximal muscle wasting andweakness, diminished reflexes, EMG abnormalities,a raised creatine kinase (Case 1) and an abnormalmuscle biopsy (Case 2). The results of the biopsyagreed with those of Norwegian investigators whoshowed predominant Type 2 muscle fibre atrophy intwo series of women with anorexia nervosa who hadsevere weight loss.67 They thought it unlikely thatthe muscle atrophy was simply due topolyneuropathy. Dastur etal,8 looking at musclechanges in adults and children with protein malnut-rition in Bombay, found that both types (1 and 2) ofmuscle fibre were smaller and myelinated nerveswere reduced in size. The evidence for neuropathyin our patients was electrophysiological, butincluded absent ankle jerks in Case 1. There were

no sensory symptoms or signs in either patient. Ourclinical and electrical evidence is in keeping with amyopathy and neuropathy as the underlyingneuromuscular disorder in malnutrition. This couldadequately be explained by a quantitative protein-calorie malnutrition but vitamin deficiency may havebeen a factor. Thiamine, pyridoxine, nicotinamide,vitamin B2 and E and folic acid deficiencies have allbeen implicated as possible causes of neuropathy. Itis possible that, in the first patient, refeeding precipi-tated thiamine deficiency when the carbohydrateload increased the requirements and led to paralysis,tachycardia and breathlessness (for review, see ref9). In her the long history of induced vomiting mayhave contributed to low thiamine levels: unfortu-nately it was not possible to confirm this biochemi-cally. There have been a few reports of thiaminedeficiency in anorexia nervosa: Handler and Per-kin'0 reported a case of Wernicke's encephalopathyassociated with anorexia nervosa. The observationof cardiovascular and neurological deterioration onrefeeding of our patient are indications of its poss-ible contributory role. There are two protective fac-tors which may have prevented thiamine deficiencyin our second patient. He was vegetarian and hadnot vomited to induce weight loss; also his calorieintake in the first three weeks of admission waslower than in Case 1. The contribution of the otherB vitamins to the neuropathy is uncertain. VitaminE and B12 levels were normal. Serum folic acid wasonly slightly low in both patients.The skin and haematological changes can be con-

sidered together. The purpuric rash in both patients,however, was difficult to explain in the presence ofonly minor thrombocytopenia on admission. In thefirst patient, but not in the second, the platelet countfell to a level consistent with purpura. In the secondWorld War studies in the Warsaw Ghetto,"Lubarsch described severe damage of capillary ves-sels leading to petechiae and oedema. It may be

that, in our patients, protein malnutrition exacer-bated by reduction in platelet levels caused the pur-puric rash.The haematological changes were of transient

bone marrow aplasia causing thrombocytopenia,anaemia and leucopenia with a spontaneous recov-ery. Warren and van der Wiele'2 looked at 42 ado-lescent girls with anorexia nervosa: 38% had whitecell counts of less than 5,000/mm3: 33% had pan-cytopenia (with platelets less than 52,000/mm3) and7% had anaemia alone. Thirteen out of 42 cases hadbone marrow biopsies: of these six were hypoplasicbut, interestingly, four out of six had no peripheralblood abnormalities. One had pancytopenia and theother leucopenia. The hypoplasia of the marrow wasalso found in Mant and Faragheres study of sixanorexic patients.'3 They considered the throm-bocytopenia unimportant in contrast to our impres-sion that it contributed to the skin changes in ourpatients. They commented that red cell aplasia is afairly common finding in marasmus and kwashior-kor, and protein depletion is considered to be themain cause either by inducing primary bone marrowabnormality or through reduced erythropoetin pro-duction. The pancytopenia of anorexia nervosa maybe due to other nutritional deficiencies perhapsrelated to reduced fat and carbohydrate ingestion.The opinion formed by Netherlands workers dur-

ing the famine in 1944-451' was that vitamin defi-ciency did not appear to be causally responsible forthe disorder in their famine victims after ninemonths' severe malnutrition and that general refeed-ing was the most effective remedy.The causes of the mild and transient liver and

renal abnormalities in the first patient after refeed-ing are uncertain. No biopsies were performed. Thereport on the effects of starvation in the WesternNetherlands'4 during 1944-1945 refers to theobservations of Pompe who looked at liver biopsiesof malnourished people and showed an absence ofglycogen in 17 out of 22 cases with focal necrosisand hydropic swelling. In our patient an obstructivepicture with some hepatocellular involvement issuggested by the raised alkaline phosphatase,glutamyl transpeptidase and aspartate transaminase.It is possible that this was due to liver dysfunctionsecondary to cardiac failure but refeeding may alsohave led to the development of a transient fattyliver.Although it is rare for patients with anorexia and

bulimia nervosa to become so acutely ill, the occurr-ence of two similar cases presenting to one clinicalunit within 6 months, indicates that it may be morecommon than the absence of reports in the literaturesuggests. The presence of a purpuric rash may be agrave warning of impending decompensation and an

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indication of the degree of malnutrition. An ade-quate dietary history will reveal those patients pro-tected from vitamin deficiency by "health food"with a conscious use of supplements. However, itseems probable that protein and carbohydrate depri-vation are responsible for the most serious pathol-ogy and vitamin deficiency may only, as in the caseof thiamine, be revealed on refeeding. The presenceof vomiting over long periods may also have beena contributory factor. It was gratifying that bothour patients recovered completely from theneuromyopathy within three months. The rash andhaematological abnormalities remitted morerapidly. In the War studies on malnutrition" 1' thecourse of recovery showed an average of 14 kgweight gain in 3 months; muscle tissue was regener-ated by exercise and the neuropathy resolved slowly,leaving paresthesiae. These residua were not seen inour patients.The severity of these patients' conditions and

potential consequences, coupled with their rapidand complete recovery in hospital, is an importantreminder of the need to admit and treat before rapiddecompensation occurs. The need to refeed slowly,at a rate inversely proportional to the severity ofweight loss is also emphasised.

The authors thank Dr R O'Brecht and Dr J Payanfor the electrophysiological studies, Dr P Guha forthe muscle biopsy report, and the PathologyLaboratories of the Maudsley and King's CollegeHospitals for the haemotology tests.

References

Russell GFM. Bulimia nervosa, an ominous variant of

Alloway, Reynolds, Spargo, Russell

anorexia nervosa. Psychol Med 1979;9:429-48.2 Gull WW. Anorexia nervosa (Apepsia hysterica,

Anorexia hysterica). Transactions of the ClinicalSociety of London 1874;7:22.

Lasegue, C. De l'anorexie hysterique. Archives ofGeneral Medicine 1873;1:385. (Also On hystericalanorexia. Medical Times 1873;2:265.)

4 Garfinkel PE, Garner DM. Anorexia Nervosa, a Mul-tidimensional Perspective. New York: Brunner/Mazel1982.

Dubowitz V, Brooke MH. Muscle Biopsy. A ModernApproach. London: WB Saunders. 1973:74-102.

6 Sletteb0 M, Lindboe CF, Askevold F. The neuromus-cular system in patients with anorexia nervosa:electrophysiological and histologic studies. ClinNeuropathol 1984;3: 217-24.

Lindboe CF, Askevold F, Sletteb0 M. Muscle changes inskeletal muscle of young women with anorexianervosa. Acta Neuropathol (Ber) 1982; 56:299-302.

Dastur DK, Daver SM, Manghani DK. Changes inMuscle in Human Malnutrition with an Emphasis onthe Fine Structure in Protein-calorie Malnutrition.Progress in Neuropath. Vol. V. Zimmermann HH, ed.New York: Raven Press, 1979.

Spillane JD, Riddoch G. Nutritional Disorders of theNervous System. Edinburgh: E & S Livingstone, 1947.

10 Handler CE, Perkin GD. Anorexia nervosa and Wer-nicke's encephalopathy: an undiagnosed association.Lancet 1982;2:771-2.

Winick M, ed. Wiley Series Current Concepts in Nutri-tion: Hunger diseases. Vol. 7, 1979.

12 Warren MP, Van der Wiele, RL. Clinical and metabolicfeatures of anorexia nervosa. Am J Obstet Gynecol1973; 117:435-49.

3 Mant MJ, Faragher BS. The haematology of anorexianervosa. BrJ Haematol 1972;23:737.

Burger ECE, Drummond JC, Stanstead MR. eds. Mal-nutrition and starvation in Western Netherlands. Sept1944-July 1945. The Hague General State PrintingOffices. 1948.

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