Giant Cell Arteritis of the Cervical Radicular Vessels Presenting with Diaphragmatic Weakness

J Neurol Neurosurg Psychiatry 1999;67:223–226 223

SHORT REPORT

Giant cell arteritis of the cervical radicular vessels presenting with diaphragmatic weakness

E A Burton, J B Winer, P C Barber

Abstract were no symptoms referable to the cranial The clinical and histopathological details nerves or legs, and no other historical features of a patient who succumbed to giant cell of note. arteritis (GCA) of the cervical radicular General physical examination disclosed di- vessels are described. The initial clinical minished chest expansion and paradoxical presentation, with diaphragmatic weak- movement of the abdominal wall on inspira- ness, has not previously been reported. tion, but was otherwise normal. Vital capacity Normal inflammatory indices and the was 700 ml standing, but the patient was unusual presentation prevented diagnosis unable to lie down because he became during life, but GCA should be considered dyspnoeic and distressed. He was alert and ori- in the diVerential diagnosis of any unex- ented, and the cranial nerves were unremark- plained neuropathic or radiculopathic able. There was mild weakness of neck flexion. syndrome, as corticosteroid therapy may There was severe asymmetric wasting of all lead to recovery. This is the first account muscle groups in both arms with fasciculation of the pathological findings in cervical and weakness commensurate with the degree radiculopathy associated with GCA. of wasting: all movements were possible against (J Neurol Neurosurg Psychiatry 1999;67:223–226) gravity but not resistance, with the exception of right shoulder abduction, which was not possi- Keywords: giant cell arteritis; radiculopathy; diaphragm ble against gravity, and left elbow flexion, extension, and wrist flexion, which were possi- Giant cell arteritis (GCA) is a common, treat- ble against resistance, but weak. There was no able condition. In this paper, we describe a wasting of the leg musculature, but occasional previously unreported clinical presentation of fasciculation was visible in both quadriceps. GCA; the diagnosis was made postmortem. It There was mild weakness of hip flexion but is important to consider GCA in the diVeren- lower limb power was otherwise preserved. tial diagnosis of any unexplained neuropathic Sensory examination was normal to all modali- or radiculopathic syndrome, as treatment may ties throughout. The deep reflexes were absent University of Oxford, apart from the right knee jerk, which was Department of Human avert the inexorable decline that we found in Anatomy and this case. This is the first published account of diminished. Both plantar responses were Genetics, South Parks the pathological features of GCA-associated flexor. Coordination was consistent with the Road, Oxford cervical radiculopathy. degree of weakness in the upper limbs, and OX1 3QU, UK normal in the lower limbs. The gait was E A Burton unremarkable. Case history Investigation showed hyponatraemia University + Department of Clinical A 69 year old man presented witha1yearhis- (Na 123 mMol/l, serum osmolality 252 Neurology tory of increasing exertional dyspnoea and mOsm/l, urine osmolality 257 mOsm/l) and J B Winer orthopnoea, and a 6 month history of upper evidence of previous anterior myocardial in- limb weakness. The dyspnoea had followed an farction on electrocardiography. The remain- Department of acute myocardial infarction, and was initially der of the routine biochemical and haemato- Neuropathology, Queen Elizabeth thought to represent pulmonary oedema. The logical profiles, including thyroid function and Hospital, symptoms failed to respond to treatment for serum electrophoresis, were unremarkable. Birmingham, UK heart failure, however, and echocardiography Antibodies to acetylcholine receptors and gan- P C Barber and coronary angiography showed relative gliosides were not detected. Hexosaminidase A preservation of left ventricular function. The concentrations were normal. Genetic studies Correspondence to: Dr J B Winer, University upper limb weakness was initially a much less excluded expansion of the trinucleotide repeat Department of Clinical prominent symptom than dyspnoea, but was associated with X linked spinal and bulbar Neurology, Queen Elizabeth progressive and bilateral. At presentation he muscular atrophy. Analysis excluded intoxica- Hospital, Birmingham B15 2TH, UK. Telephone 0044 had been unable to perform fine manipulative tion with lead, manganese, thallium, or arsenic. 0121 472 1311. tasks or lift his arms above his head for about 2 No porphyrin or porphobilinogen was detected months. In addition, he had noted cramp-like in the urine, which was acellular and without Received 6 July 1998 and in sensations in the right arm, and had seen the casts. revised form 3 February 1999 muscles “flickering” on occasions, but there Chest radiographs showed bilateral raised Accepted 10 February 1999 was no sensory loss or paraesthesiae. There hemidiaphragms, but normal heart size, and no 224 Burton, Winer, Barber

focal collapse or consolidation. Abdominal and glucose of 4.6 mMol/l. Abnormal IgG ultrasound and CT examinations were unre- bands were detected in serum and CSF—the markable, as was MRI of brain, whole spine, pattern was identical in both, suggesting and brachial plexus. His CSF was acellular and peripheral IgG synthesis. Biopsy of the right sterile, with a protein concentration of 0.12 g/l deltoid muscle showed histological features in keeping with chronic denervation (ﬁgure A); biochemical assays were normal. Electrophysiological investigation showed normal sensory studies and motor conduction velocities. Reduced compound muscle action potential amplitudes were seen in the upper and lower limbs (for example, right median nerve at wrist to abductor pollicis brevis: 3 mV), and F wave latencies were prolonged with reduced frequencies. Electromyographic sam- pling showed evidence of denervation in muscles of all four limbs. Additional studies excluded the presence of proximal conduction block and showed normal central motor conduction. On admission, the erythrocyte sedimentation rate (ESR) was 25 mm/h. He subsequently developed a persistent low grade fever and ris- ing ESR (table). Assisted mechanical ventila- tion was instituted to alleviate respiratory embarrassment caused by weakness of the respiratory muscles. Unfortunately, he continued to deteriorate and died of respiratory failure.

POSTMORTEM EXAMINATION General postmortem examination showed evidence of previous myocardial infarction and coronary artery atheroma, but no other abnormality. Examination of the spinal cord showed diVuse pallor of myelin with minor loss of anterior horn cells. Scattered cells showed central chromatolysis indicative of acute axonal damage. The changes were most marked at the cervical level. Nerve roots showed patchy axonal loss and fibrosis consistent with ischaemic injury (figure B). Dorsal root ganglia showed neuronal loss with many ganglion cells undergoing degeneration with associated ag- gregates of lymphocytes and macrophages (figure C). Scattered small blood vessels associated with spinal nerve roots had lymphocytic cuVs, and radicular arteries of the lower cervical roots and their branches displayed a florid giant cell arteritis with a dense infiltrate of lymphocytes and macrophages plus multinucleate giant cells throughout the media, destroying the muscle and internal elastic lamina and associated with intimal fibroblastic proliferation (figure C, D). Peripheral nerves, including brachial plexus and femoral and median nerves were exam- (A) Biceps brachii, paraYn wax section, showing small ined. A few fascicles showed evidence of axonal group fibre atrophy indicative of chronic denervation. Blood vessels in the muscles examined showed no evidence of loss with corresponding fibrosis. Some of the inflammatory changes. (Haematoxylin and eosin associated blood vessels showed cuVs and × originally 140.) (B) Part of a cervical nerve root, occasional infiltrates of lymphocytes. A single immunostained with an antibody to CD68 antigen, showing many macrophages within the tissue indicative of active fibre breakdown and phagocytosis. (Immuno- Measurements of erythrocyte sedimentation rate (ESR) at peroxidase originally×140.) (C) Radicular artery branch various time points after admission to hospital adjacent to C6 dorsal root ganglion, showing active giant cell arteritis. Part of the ganglion is visible in the right of the field. (Haematoxylin and eosin originally×35.) (D) Detail Days after admission ESR (mm/h) from the same artery as above, showing dense mixed 025 chronic inflammatory cell infiltrate, destruction of the 13 69 internal elastic lamina with associated giant cells, and 42 100 marked intimal thickening. (Haematoxylin and eosin 60 114 originally×140.) Giant cell arteritis of the cervical radicular vessels presenting with diaphragmatic weakness 225

meningeal vessel showed lymphocytic infiltra- patient had developed motor neuron disease, tion of the intima and adventitia, but thorough although the reported clinical features are examination of blood vessels elsewhere showed atypical and postmortem examination was not no abnormality. carried out. The association of motor neuropathy and GCA is not definite in a further Discussion case in which the neuropathic features started The histopathological abnormalities seen in to resolve before the introduction of steroid blood vessels supplying the cervical cord and therapy.16 Further cases of GCA associated nerve roots suggest two possible diagnoses: with C5 radiculopathy are reported without extracranial giant cell arteritis (GCA) and details53 as are two cases of unilateral arm granulomatous angiitis of the central nervous weakness.4 system (GANS). We favour the first diagnosis The present case is unique for several for two reasons: Firstly, GANS is almost always reasons: Firstly, the initial symptom was confined to the CNS,12 but the most impres- dyspnoea, caused by diaphragmatic weakness. sive histological changes in this case were in This has previously been described in only a radicular arteries rather than the vessels within single case of GCA, as a later component of a or supplying the cord, and there was evidence more extensive clinical picture involving the of involvement of tissues (peripheral nerves) brainstem and oculomotor nerves.13 Respira- remote from the CNS. Secondly, the lesions tory presentation is, however, well recognised themselves showed intense inflammation and in other diseases aVecting the motor neurons of focal destruction of the media, which is typical the cervical cord and their axons.17–20 Secondly, of GCA3; lesions in GANS are commonly there are no other reported patients with GCA reported to spare the media.1 associated radiculopathy or neuropathy of this We suggest that this patient succumbed to a severity in whom constitutional symptoms, severe form of GCA, restricted mainly to abnormalities of the temporal pulses, and vessels supplying the cervical nerve roots, raised ESR were all absent at presentation, resulting in motor axonal injury secondary to making diagnosis in the present case extremely radicular ischaemia. This led to denervation diYcult. This was further confounded by the and weakness of the upper limbs and dia- resolute normality of the sural sensory nerve phragm (as evidenced by the presence of para- action potentials throughout the illness, pre- doxical movement of the abdominal wall on cluding sural nerve biopsy. Finally, this is the respiration, extremely low vital capacity associ- first case of GCA associated radiculopathy in ated with orthopnoea, and bilateral raised which histological examination of the spine hemidiaphragms on chest radiographs). Rela- and spinal nerve roots has been undertaken, tively mild histopathological abnormalities facilitating understanding of the pathological present in the lumbosacral expansion and lum- process. bar nerve roots were associated with mild clini- It is established that severe involvement of cal and electrophysiological abnormalities in the vertebral arteries is a common pathological the legs. The coronary arteries were not exam- finding in GCA without peripheral nervous ined histologically, so it is not possible to state system disease.21 The cervical cord and roots whether myocardial infarction was a result of derive their blood supply from the vertebral coronary angiitis. vessels. It has been proposed that the mech- The association of GCA with disease of the anism of cervical root damage in GCA is peripheral nervous system is well recognised, ischaemia secondary to hypoperfusion through although the incidence has been variously stenosed vertebral arteries,10 and that the anat- reported as 1.1%-14%.3–5 The commonest pat- omy of the radicular vasculature may help terns of abnormalities seen are symmetric sen- explain the tendency for the midcervical roots sorimotor polyneuropathy (usually mild and to be preferentially aVected.13 Angiographic chronic),5–7 and single or multiple mono- stenoses of the ipsilateral vertebral artery were neuropathy.58 showed in one case of GCA associated C5 Neuropathy and radiculopathy with severe radiculopathy,12 but the authors of this report motor impairment associated with GCA is less expressed doubt that the lesions could account well described. Details of six cases of cervical for ischaemic nerve root injury on account of radiculopathy have been reported.9–13 The C5 the rich collateral blood supply to cervical root was aVected in all; the abnormalities were nerve roots. Our findings provide an alternative purely motor in four of the cases. There are two explanation. We have demonstrated florid reported cases714 of generalised proximal arteritis of the radicular vessels themselves, weakness and wasting associated with EMG rather than proximal feeding vessels, as the evidence of denervation; these may also have cause of ischaemic radiculopathy in this been radiculopathic in origin. All eight of these patient. Furthermore, we found no evidence of patients had raised ESR at diagnosis, and direct extension of the inflammatory process improvement of neurological impairment with into the brachial plexus, as suggested in one corticosteroid therapy was universal. There is a report.11 It is possible that previously reported single case report of a patient with typical poly- cases of cervical radiculopathy had a similar myalgia rheumatica and raised ESR, who went pathological basis to the present case. An on to develop symmetric lower motor neuron analogous mechanism seems to be true of weakness, including the facial nerve distribu- peripheral nerve, where axon damage in GCA tion, in association with brisk reflexes, an associated neuropathy has been reported to extensor plantar reflex, and mild sensory result from ischaemia arising from occlusion of abnormalities.15 It was suggested that the the nutrient arteries to peripheral nerves, both 226 Burton, Winer, Barber

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