Rapid Shaking Body—A Novel Phenomenon of Anti‐GAD Ab Induced Stiff Person Syndrome and its Electrophysiological Findings

Stiff person syndrome (SPS) is a rare autoimmune disorder characterized by central nervous system hyperexcitability, muscle stiffness and spasms, often associated with anti‐glutamic acid decarboxylase 65 (anti‐GAD65) antibodies. ¹ , ² SPS and related anti‐GAD disorders show heterogeneous clinical features, making diagnosis challenging and necessitate multimodal approach integrating clinical findings, serological and cerebrospinal fluid studies, ³ , ⁴ as well as electrophysiological tests which play a key role in demonstrating CNS hyperactivity and supporting clinical observations in SPS. ⁵ We describe a novel phenomenon of “rapid shaking body” as a presentation of anti‐GAD associated SPS and further confirm it being pathological by electrophysiological studies.

Case Report

A 41‐year‐old woman with history of hyperthyroidism presented with new‐onset involuntary movements. Approximately 3 weeks before consultation, she began experiencing episodic involuntary movements involving the lower limbs and pelvic region, each episode lasting about 20 seconds and typically resolved spontaneously. Over time, the frequency and severity of the involuntary movements increased, yet she remained conscious and retained memory throughout the episodes. She subsequently visited the emergency department due to prolonged episodes lasting up to 20 minutes. Neurological examination revealed no weakness or cranial nerve palsies, with normal deep tendon reflexes and negative Babinski sign. However, abnormal truncal movements were frequently triggered by changes in body position. The episodes, lasting from seconds to several minutes, were characterized by painful, tremulous movements predominantly affecting areas below the mid‐torso, including the back, abdomen, pelvis and lower limbs (Video 1).

VIDEO 1.

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Segment 1. The patient exhibited painful, tremulous movements predominantly involving the mid‐to‐lower trunk—including the back, abdomen, pelvis, and bilateral lower limbs—when attempting to transit to a lateral decubitus position from supine posture. Segment 2. The “rapid shaking body” movements were easily and frequently triggered by changes in body position during electrophysiological testing.

EEG was normal without captured shaking episodes, and brain CT and spinal MRI were unremarkable. Cerebrospinal fluid analysis was not performed due to safety concerns.

Multi‐channel surface electromyography (sEMG) recordings were obtained from muscles including the soleus, tibialis anterior, biceps femoris, rectus femoris, rectus abdominis, longissimus thoracis and sternocleidomastoid muscles. Semirhythmic trunk movements were frequently provoked by positional changes. The sEMG revealed synchronized 10–12 Hz EMG bursts, with 35 ms burst duration over truncal and proximal lower extremity muscles without rostral spreading above sternocleidomastoid muscle (Fig. 1A). The phenomenon involved synchronized contractions of both agonist and antagonist muscles, such as the rectus abdominis and longissimus thoracis paraspinal muscles, while cranial and proximal upper extremities muscles remained unaffected. The EMG power spectrum showed a 10 Hz peak and up to 0.9 coherence in the longissimus thoracis and rectus abdominis, indicating a common tremor generator (Supplementary Fig. S1). EMG onset in the longissimus thoracis preceded lower limb muscles (tibialis anterior, soleus) by 14 ms (Supplementary Fig. S2). Exteroceptive stimulation was performed with tibial nerve stimulated in train‐of‐four pulses (200 μs duration, 3 ms interval) at three times the sensory threshold, which elicited a long‐lasting tonic activity in the lower limb muscles followed by gradual decrescendo of activity (Fig. 1B). The blink reflex recovery cycle test in left eye showed 71% inhibition of the R2 response at a 200 ms inter‐stimulus interval (Fig. 1C), suggesting preserved brainstem inhibitory circuits. Together, these findings indicated pathological hyperexcitability localized predominantly within the spinal cord with minimal brainstem involvement.

Fig 1.

Electrophysiological findings before and after treatment. (A) Multi‐channel surface electromyography (sEMG) revealed semi‐rhythmic 10–12 Hz EMG bursts provoked by positional changes (red vertical dashed line) especially in the left longissmus thoracis, rectus abdominis, soleus, and tibialis anterior muscles. (B) Exteroceptive stimulation elicited sustained tonic activity in all recorded muscles of trunk and lower limbs lasting for 200 ms. (C) Blink reflex recovery cycle test recorded from the left eye showed 71% inhibition of the R2 response (green dashed arrow) at a 200 ms inter‐stimulus interval. The black arrow indicated R1 responses. The follow‐up electrophysiological tests 4 months after therapy showing profound reduction of the semi‐rhythmic EMG bursts after positional change (red vertical dashed line) (D), and restored responses to the exteroceptive stimulation (E).

Biochemical analyses demonstrated markedly elevated free T4, undetectable thyroid‐stimulating hormone, high titers of anti‐thyroid peroxidase antibodies and thyroglobulin antibodies, compatible with primary hyperthyroidism with an autoimmune etiology. Additional basic autoimmune and oncological screenings yielded no abnormal findings. Type 1 diabetes mellitus was also excluded. Given the clinical features of spinal hyperexcitability, we tested for autoantibodies including anti‐GAD65 and anti‐amphiphysin, which revealed strong seropositivity for anti‐GAD65 (intensity 66, positive 3+, immunoblot assays). Taking into account the clinical features and electrophysiological findings, the diagnosis of SPS is favored. Treatment with diazepam (5 mg four times a day) and pregabalin (75 mg twice a day) reduced the frequency and severity of the rapid body shaking episodes to once per week. Although tremor lessened, she still felt tremor, stiffness and anxiety. After discussing options, she received two doses of 1000 mg rituximab which led to marked improvement. A follow‐up electrophysiological study conducted 4 months after treatment showed reduction in truncal tremors on sEMG (Fig. 1D) and normalization of responses to exteroceptive stimulation (Fig. 1E). These findings paralleled her clinical improvement.

Discussion

The “rapid shaking body” was characterized by approximately 10–12 Hz synchronized contractions of the abdominal and paraspinal muscles, with a caudal spread to the lower limbs yet without rostral involvement above the sternocleidomastoid muscle. In this case the exteroceptive stimulation represented exaggerated responses, which are considered hallmark feature of SPS, ⁵ while the blink recovery cycle demonstrated normal suppressive responses, suggesting intact brainstem reflex circuits thus localizes the pathological origin to the spinal cord in this distinct presentation. Abnormal EMG activity began in the longissimus thoracis and rectus abdominus, 14 ms before soleus and tibialis anterior activation, consistent with symptoms starting from the back and spreading to the legs. This implies mid‐ to lower‐thoracic spinal cord involvement, though the exact level remains uncertain. SPS likely affects selective GABAergic circuits rather than the entire CNS and possibly spares brainstem inhibitory pathways. ⁶ We speculate that sensory inputs, such as positional changes, triggered abnormal co‐contractions from partial dysfunction of presynaptic GABAergic interneurons in the thoracic cord. Intact descending brainstem inhibition may have limited continuous muscle contractions, producing an “active‐suppressive‐active” EMG pattern that appeared clinically as tremor‐like bursts instead of sustained spasm. Taken together, the “rapid shaking body” phenomenon may be deemed as part of the clinical spectrum of anti‐GAD65 associated SPS which primarily results from hyperexcitability of the spinal cord. Our findings also align with recent proposals advocating the use of integrated electrophysiological assessments, such as sEMG, exteroceptive stimulation and brainstem circuits evaluation performed in our case, as essential criteria for diagnosing stiff person spectrum disorders and monitoring treatment responses. ⁷ , ⁸

Author Roles

(1) Research project: A. Conception, B. Organization, C. Execution, D. Patient care; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique;

C.C.W.: 1A, 1B, 1C, 3A

C.Y.C.: 1B, 1C

Y.S.D.: 1B, 1C

K.S.C.: 1A, 1B, 1C, 1D, 3B

Disclosures

Ethical Compliance Statement: All investigations performed were done during clinical practice and patient care. The authors confirm that the approval of an institutional review board was not required for this work according to the operational guidance of our institute. The authors confirm that written informed consent for the publication of the medical data and the video were obtained from the patient. Written consent is with the authors. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding and Conflict of Interest Statement: No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the previous 12 months: The authors declare that there are no additional disclosures to report.

Supporting information

Figure S1. Surface electromyography, power spectrum, and coherence plots of longissimus thoracis and rectus abdominis muscles. The electromyography (EMG) demonstrates synchronous burst activity between the two muscles (left, dotted red arrows). This synchronicity corresponds to the fundamental 10 Hz peaks observed in the power spectra (upper and middle right) with a high coherence value of up to 0.9 between the two muscles (bottom right).

Figure S2. Surface electromyography (sEMG) recorded from the left longissimus thoracis, rectus abdominis, sternocleidomastoid, soleus, tibialis anterior, biceps, and rectus femoris muscles. The multi‐channel sEMG revealed burst onsets beginning in the longissimus thoracis and rectus abdominis muscles, followed 14 ms later by activation of lower limb muscles including the soleus and tibialis anterior.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.