Stiff-Person Syndrome: Revitalizing Recovery with Modafinil for Fatigue and Function

Case Diagnosis: Stiff Person Syndrome

Case Description or Program Description: A 67-year-old female with anti-amphiphysin antibody-positive Stiff-Person Syndrome (SPS) was admitted to inpatient rehabilitation with weakness and dyspnea following IVIG. She was diagnosed with acute hypoxic respiratory failure secondary to pulmonary embolism, on full dose Lovenox. During her acute inpatient rehabilitation stay, Modafinil 100mg/day was initiated due to severe fatigue. Modafinil resulted in significant improvement in cognition, motivation, participation and alertness. Paraneoplastic etiology was considered due to positive anti-amphiphysin antibodies, and elevations of CEA and CA; however, repeat values were normal, and no malignancy was found.

Setting: Acute inpatient rehabilitation center.

Assessment/Results: On admission, the patient had 0/5 strength in bilateral upper and lower extremities, severe dysarthria, and profound fatigue, requiring total assistance for ADLs. Following inpatient rehabilitation and Modafinil initiation, with improvement in strength to 3/5, functional speech, cognition, mood, and appetite. Enhanced wakefulness facilitated greater participation, significantly improving functional independence and quality of life, allowing her to progress to outpatient therapies.

Discussion (relevance): SPS is a rare neurological disorder characterized by progressive muscle rigidity, spasms, and exaggerated startle responses. While motor dysfunction is well-recognized, fatigue and cognitive impairment are often overlooked, limiting rehabilitation participation. Current treatments to reduce rigidity include benzodiazepines and immunotherapy. However, they may exacerbate fatigue and cognition. Our case highlights Modafinil as a novel approach to SPS-related fatigue, enhancing wakefulness without worsening muscle rigidity. Unlike amphetamines, which increase muscle tone, spasms, and cardiovascular strain, Modafinil selectively activates orexin pathways, improving alertness without excessive sympathetic stimulation.

Conclusions: This case highlights the significant impact of SPS-related fatigue and the potential role of Modafinil in enhancing rehabilitation outcomes. By improving wakefulness, cognition, and engagement in therapy, Modafinil facilitated functional gains and independence. Targeted fatigue management should be considered in SPS treatment to optimize patient recovery and quality of life.