Utility of Botulinum Injections in Stiff-Person Syndrome

Case reports in neurology
18 Nov, 2019 ,

Stiff-person syndrome (SPS) is an uncommon neurological disorder characterized by significant rigidity and muscle spasms primarily affecting the truncal and proximal musculature. Furthermore, a wide-based gait with functional impairment is generally seen. High-dose benzodiazepines or baclofen are widely considered the optimal initial therapy; however, major adverse effects often preclude adequate dosing. Refractory cases may be treated with intravenous immunoglobulins (IVIG), plasma exchange, or B-cell depletion with rituximab, although these are also associated with major, sometimes fatal, adverse reactions. Several reports have validated the safety and utility of botulinum injections in this setting, yet botulinum remains markedly underutilized in this cohort. This case report shows that botulinum can decrease pain and stiffness, improve gait and balance, and decrease dependence on powerful systemic treatments in this group.

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 A 38-year-old female with anxiety, depression, and Grave's disease presented with several months of diffuse muscle pain and spasms. She had previously been diagnosed with hyperthyroid myopathy as well as rhabdomyolysis. Repeat CK level in the clinic was normal, as was MRI of the brain and cervical spine, EMG/nerve conduction study, aldolase, autoimmune panel, and muscle biopsy. Notably, anti-GAD antibodies were negative in the serum at that time. One year later, she returned with a progressive worsening of her symptoms, including impaired ambulation, difficulties with activities of daily living, and hospitalizations to manage pain. Repeat serum anti-GAD-65 antibodies were 69 IU/mL (normal <5 IU/mL).

EMG revealed continuous motor activity in several muscles of the neck and thoracic paraspinal muscles, where she reported significant pain and tightness. Her symptoms were not sufficiently controlled on a combination of diazepam 7.5 mg three times a day, baclofen 30 mg three times a day, Percocet 10–325 mg four times per day, tizanidine 4 mg three times a day, IVIG 400 mg/kg every 4 weeks, and physical therapy. Her initial Botox treatment consisted of 25 units Botox in the right as well as left trapezius, and 25 units in the right and left sternocleidomastoid muscle. Three months later she had a second treatment in which those dosages were exactly doubled (50 units in the right and left trapezius and 50 units in the left and right sternocleidomastoid muscles).

Again, three months afterwards she received 50 units in the right and left trapezius and sternocleidomastoid muscles as well as 20 units in the right as well as left thoracic paraspinals as she noted pain and spasms in that region. 6 months later she received 40 units in the right and left trapezius, 40 units in the right and left levator scapulae, and 30 units in the right and left semispinalis capitis muscles. The Botox dosages were adjusted each treatment to target the most painful regions at that time. After the addition of Botox injections, the patient reported an improvement in pain, decreased muscle spasms, an improvement in her quality of life, although she was not able to decrease her home medications. She denied adverse effects from the Botox treatments.

In 2003, Szczepańska-Szerej et al. reported a marked functional improvement and a decreased dependence on systemic drugs for up to four months in a 41-year-old woman with SPS following botulinum injections. Similarly, Shah and Bunzol described a 53-year-old-male with stiff-person syndrome with a poor response to IVIG, corticosteroids, diazepam, baclofen, gabapentin, warm baths, heating pads, transcutaneous electrical nerve stimulation, and chiropractic manipulation. Following botulinum injections to the biceps femoris, adductor magnus, and rectus femoris, the patient reported considerable pain relief, improved range of motion, and decreased stiffness. He also noted an improvement in balance and gait with fewer falls and the ability to walk longer distances.

Likewise, in 1993, Davis and Jabbari reported remarkable relief from pain and stiffness and a substantial improvement in ambulation in a 36-year-old male with stiff-person syndrome after botulinum injections into the lumbar paraspinal muscles. The patient suffered from an awkward and antalgic gait and was unable to stand from the sitting position without assistance due to marked stiffness and pain. EMG noted continuous activity in the lumbar paraspinals, which were injected with a total of 560 units of botulinum toxin after diazepam and baclofen provided only minimal relief. The injections were done over three sessions spanning three weeks and were divided over five sites from L1–L5. One week after the final set of injections, the patient noted almost complete relief from exertional pain and resolution of painful spasms. The injections also lead to a significant functional improvement and reduced need for systemic drugs.

Botulinum injections have also been shown to improve rigidity, pain, and gait in stiff-limb syndrome. In 2012, Anagnostou and Zambelis recounted a 40-year-old female with several years of progressive stiffness of the left leg. Modified Ashworth scale score of the extremity was four, signifying that the affected extremity was rigid in flexion or extension, and EMG showed continuous motor unit potentials in the left vastus medialis. Following a poor response to pharmacotherapy, several dosages of Botox were tried over time without significant subjective improvement. Ultimately, a dose of 900 units (vastus lateralis 350 units, vastus medialis 350 units, and rectus femoris 200 units) produced a marked improvement in her symptoms.

She reported a dramatic improvement in rigidity and gait as well as decreased pain for two and a half months following the injections. Modified Ashworth scale score following the injections was one, denoting a slight increase in muscle tone, and repeat EMG was within normal limits. She denied adverse effects other than a slight weakness of leg extension, which she noticed only when attempting to jump. Three months following the injections, her symptoms had returned. She repeated the injections at the dose of 900 units and again reported a dramatic improvement in her symptoms.