Spinal cord ischaemia following the gluteal injection of Benzathine benzylpenicillin

Abstract

Introduction

Spinal cord injury is a devastating complication, though rare but possible following the intramuscular injection of the Penicillin. The spinal cord injury can be permanent, leaving the patient with paralysis, bowel and bladder incontinence, and with other associated morbidities.

Case presentation

We report a 25-year-old gentleman who developed anterior spinal cord syndrome following the benzathine benzylpenicillin injection. In this case report, we discuss the clinical details, possible hypothesis behind spinal cord ischaemia and literature review.

Discussion

Spinal cord ischaemia or infarction occurs due to embolism of the Penicillin products. The products following injection are carried as emboli retrogradely through the superior gluteal artery and can cause infarction to the cord’s anterior part.

Spinal cord ischaemia is a rare complication following the gluteal injection of Benzathine benzylpenicillin. The hypothesis is embolization of the Penicillin products retrogradely through the Superior gluteal artery and cause occlusion of the vasculature that supply the spinal cord. This article includes literature review of the hypothesis behind the Spinal cord ischaemia and highlights the previous cases reported.

Introduction

Spinal cord injury is a rare complication reported following intragluteal injection of Benzathine benzylpenicillin. This has been reported to cause irreversible Paraplegia depending on the extent of involvement of the spinal cord. We present a 25-year-old gentleman who presented to a local Sexual health clinic with a 2-week history of a right-sided lump in the inguinal region. He was treated with intramuscular Benzathine benzylpenicillin into both the gluteals. Within 5–10 min, he developed bilateral lower limb weakness, paraesthesia and excruciating lower back pain. He attempted to stand up, but his legs collapsed with sudden bladder and bowel incontinence. MRI scan showed cord ischaemia from T10 level down with associated conus injury. This gentleman made slow but progressive recovery of lower limb function and complete recovery of both bladder and bowel. We report this case to create awareness that, although rare, it is still possible and has been reported in the past as well.

Case presentation

The 25-year-old gentleman, who was already known to a local Sexual health clinic, presented to them with a history of a right-sided lump in the inguinal region of 2 weeks duration following an alcohol binge. Following the history and the clinical examination, a diagnosis of Syphilis was made. He was offered an intramuscular injection of Benzathine benzylpenicillin into both gluteal regions. He had received intramuscular injection of Benzathine benzylpenicillin in the past for similar presentation.

Within 5–10 min following the injection, he developed bilateral lower limb weakness, severe paraesthesia involving both lower limbs, and excruciating lower back pain. He attempted to stand up but collapsed on the floor with sudden bladder and bowel incontinence. He developed a mild local reaction to the injection site. MRI scan was done for brain, pelvis as well as spine. MRI brain was normal. MRI spine showed an extensive longitudinal region of mildly expansive spinal cord signal involving the lower thoracic cord, including the conus covering the T10–L1 (Figs. 1 and 2). The above features were consistent with spinal cord ischaemia. MRI Pelvis showed inguinal lymph nodes with oedema in the gluteal muscles consistent with the recent administration of the intramuscular injection. MRI Spine was repeated the following day (Fig. 3), which showed restricted diffusion within the distal cord and the conus consistent with spinal cord infarction. However, there was an improvement of the cord oedema and craniocaudal extent of the cord signal change. The differential diagnosis was longitudinally extensive transverse myelitis, given the radiological picture.

Fig. 1. T2 weighted saggital MRI scan of dorsolumbar scan.

MRI scan done on day 1 (dorso-lumbar spine).

Fig. 2. MRI scan done on day 1 (lumbosacral spine).

MRI done (Figs. 1 and 2) on day 1 showed longitudinally extensive region of mildly expansile spinal cord signal abnormality within the lower thoracic spinal cord and conus covering T10–L1. The appearances suggestive of possibility of spinal cord ischaemia with differentials being longitudinally extensive transverse myelitis (LETM).

Fig. 3. MRI scan done on day 2.

The distal cord and conus showing features suggestive of cord infarction.

He had extensive biochemistry investigations, which included Electrophoresis and Immunoassay, antiphospholipid markers, thrombophilia screen, lupus anti-coagulant, antiphospholipid and anti-cardiolipin antibody screen, compliment assay, myelin oligodendrocyte glycoprotein antibodies screen, Hep2 anti-nuclear antibody test. The extensive biochemistry tests did not detect any abnormality. The Treponema pallidum antibodies were not detected. His other investigations for sexually transmitted investigations like Chlamydia, Neisseria gonorrhoea antibodies were also negative. Since this event happened during the COVID- pandemic, this was also investigated, and the result was negative.

Two months later he was admitted to the tertiary spinal rehabilitation centre for further rehabilitation. His admission neurological examination showed his level was L2 AIS C. The Neurological Classification was based on the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSI) [1]. Anal tone was present but weak with intact deep anal sensation. He was wheelchair dependent on admission and needed assistance for transfers. He required minimal assistance with his bowel and bladder management. He made a gradual recovery with respect to the motor power involving the lower limbs. He remained in the specialist spinal rehabilitation centre for 2 months. He was able to mobilise with two elbow crutches for short distances and became independent with both bladder and bowel. His discharge neurological examination showed his level progressed to L3 AIS D.

Discussion

Penicillin has been used worldwide since it was discovered by Sir Alexander Fleming in 1928. Benzathine Benzylpenicillin [2] is the first-line treatment for Syphilis and is used for Rheumatic fever, post Streptococcal glomerulonephritis prophylaxis etc. The injection should not be administered into tissues with reduced perfusion. The injection is normally given in the Hochstetter’s ventrogluteal field which is the outer quadrant of the gluteus maximus. The injection is normally given with the needle pointing towards the iliac crest according to the Hochstetter’s method. The puncture should be as vertical to the skin surface as possible and the injections as far away from the major blood vessels as possible. The other areas where the injection is given is in the mid-lateral thigh.

There are two patterns of injuries reported with the intramuscular Penicillin preparations. One is Hoigne’s syndrome [3–11] (panic attack, hallucinations, personality change, thinking disorder, feeling of impending doom, a sensation of dying, extreme fear, vertigo, tinnitus, convulsions, coma, ataxia, extraocular muscle palsy, hypertension and tachycardia), an immediate, brief central nervous system dysfunction. The second pattern of injury is immediate and frequently permanent, a combination of injuries that spans the distribution of the subdiaphragmatic arterial supply [12–14].

The hypothesis behind the thoracolumbar cord ischaemic injury is an accidental injection into the superior gluteal artery, propelling the drug retrogradely through the internal iliac artery and its lumbar branch, or through the lumbar aorta, up to the origin of the anterior spinal artery of Adamkiewicz. It is not clear if the ischaemia is due to localised arterial occlusion or extensive arterial spasm. The autopsy results of the two cases reported [15, 16] supports the localised arterial occlusion. The neurological sequelae of flaccid paralysis or muscle weakness, with sphincteric signs, were consistent with anterior spinal cord syndrome. The typical results of the occlusion of the artery of the Adamkiewicz’s artery are isolated muscle deficit, due to selective necrosis of the grey matter in the anterior horns which are particularly sensitive to ischaemia [15, 16].

Nicolau syndrome [17–23] is a rare injection site reaction following intramuscular administration of drugs with tissue damage. This was reported by Freudenthal in 1924 and later by Nicolau in 1925. The typical patient presents with intense pain around the injection site soon after the injection, followed by erythema, purplish discolouration of the skin, haemorrhagic patch, and finally, tissue necrosis with a pale marble-like pattern. It can result in cutaneous, subcutaneous, and even muscle necrosis. Nicolau syndrome was found to be associated with a spectrum of neurological manifestations ranging from transverse myelitis to nerve plexopathies [23]. Animal experimental studies using arteriography have explicated the pathogenesis of an obstructive vasculopathy, non-filling and marked vascular stasis in the superior gluteal artery and adjacent vasculature [24, 25]. The hypothesis is arterial vasospasm due to the release of vasoactive mediators. The hypothesis [25] is by damage to the end-arteries by cytotoxic effects following intra-arterial embolism of the particular drug followed by arterial vasospasm and tissue necrosis. Other hypothesis is extra-arterial compression of the supplying artery by the injected volume.

Penicillin preparations are so opaque and viscous that blood can be aspirated but can go unnoticed [26–30]. The data available [13, 14, 26–32] refer to the opacity of the preparations and the difficulty of visualising withdrawn blood in certain medication delivery systems. Opacity problems were reported by Utley et al. [11]. It is suggested that the unattached needle could be inserted and observed for 30–45 s for blood. If no blood is seen, the syringe to be attached and aspirated. It is surprising to know the frequency of finding blood at the initial needle placement was about 1 in 50 injections [14]. The injection should be given as slowly as possible with low pressure. Rubbing after the injection should be avoided.

Our patient, fortunately, made a good recovery within a few months following the spinal cord injury. In the two cases reported by Tesio et al. [15], one a 31-year-old who developed permanent flaccid paralysis, and the second patient a 9-year-old child; it took 13 years to make a partial recovery. Six similar cases were reported previously in the literature (4 adults and two children of 15 months and 4½ years) [16, 33–36]. In all of them, an intragluteal injection of Penicillin was suddenly followed by transverse myelitis. One patient died after 18 days [16] and the autopsy revealed selective haemorrhagic necrosis of the anterior horns of the lumbosacral cord. The five survivors remained paraplegic [16, 33–36]. A 20-year-old male was reported [23] who developed Nicolau syndrome and transverse myelitis after receiving the benzathine penicillin injection. At follow up, he showed partial motor recovery with no significant improvement in his sensory symptoms.

Conclusion

Spinal cord injury following Penicillin injection is rare but a possibility. Spinal cord injury can be permanent with devastating disability. Hence, those clinicians who are involved with administering the drug should exercise caution. Even from the medico-legal point of view, patients should be appropriately consented for rarer complications that can have devastating effects.

Author contributions

The authors contributed equally to this manuscript.

Competing interests

The authors declare no competing interests.

Supplementary information

The online version contains supplementary material available at 10.1038/s41394-022-00503-z.