An Uncommon Cause of Gait Disturbance and Cognitive Decline
Mrs. S, a 65-year-old Caucasian woman, presented to a primary care clinic with concerns that she was becoming progressively unsteady on her feet. Mrs. S felt that the onset of her gait change occurred around the time of her elective right total knee arthroplasty (TKA), nearly three years earlier. The patient attributed her unsteadiness and limping to postoperative “weakness” and a “lack of confidence” in her right knee. She suffered from multiple falls after her surgery but denied any serious injury. To compensate, Mrs. S had started utilizing a single-pronged cane and had withdrawn from a number of hobbies and social activities. She reported the need to use her arms to rise from a seated position. In spite of efforts to exercise, both Mrs. S and her husband, Mr. S, felt that her gait was deteriorating. At the time of this visit, she denied any upper-extremity symptoms, paresthesias, or pain.
Postoperatively, her orthopedic surgeon felt that her TKA was healing appropriately, but noted persistent gait instability at her one-year follow-up visit. At this time she was referred to a sports medicine therapist for two sessions of gait retraining. Her instability persisted for the next year and a half and led to a fall and multiple lower-extremity soft tissue injuries. This fall prompted consultations in Neurology and Physical Medicine and Rehabilitation. Mrs. S was again referred back to a physical therapist for four more sessions of functional gait re-education, without significant improvement in her gait. At this time she was also referred to a psychiatrist for management of a possible adjustment disorder. Based on all available clinical information, her limp was primarily felt to be functional and related to multiple psychosocial stressors, postsurgical deconditioning, and musculoskeletal pain from falls.
Shortly before she presented to the primary care clinic for worsening gait, Mrs. S was evaluated by psychiatry. She was noted to have difficulty recalling dates and reportedly gave contradictory information and vague responses to direct questions. Mr. S endorsed concerns about Mrs. S’s cognitive changes and described personality changes that included decreased motivation, decreased interest in socialization, and anhedonia. Upon review of systems, the patient denied changes in sleep, appetite, guilty feelings, concentration, psychomotor symptoms, or suicidal thoughts. Her psychiatrist strongly suspected cognitive impairment.
Mrs. S’s past medical history was significant for adjustment disorder, hyperlipidemia, hypertension, osteopenia, osteoarthritis, reactive airway disease, and a remote history of treated tuberculosis. She was up-to-date with colon, cervical, and breast cancer screening. Regular medications included atorvastatin 20 mg daily, lisinopril 20 mg twice daily, atenolol 100 mg once daily, and risedronate sodium 35 mg once weekly. The patient also reported taking glucosamine and chondroitin sulfate, calcium carbonate, and vitamin D. She did not use alcohol, tobacco, or recreational drugs. Mrs. S had been a teacher and had advanced degrees in education and English. She became a full-time homemaker in the 1970s. She was living at home with her husband in a small community, and they had multiple adult children and grandchildren living nearby. Her family history was negative for any history of cognitive impairment or neurodegenerative disease.
Physical examinations by her primary care physician and neurologist revealed a mildly obese woman with normal vital signs. Mrs. S had difficulty rising from her chair and required the use of her upper extremities to stand. She walked with a cane in her right (dominant) hand and was noted to have an externally rotated right lower extremity. She dragged her right foot and was unable to perform tandem steps. Cranial nerve examination was normal. Funduscopic examination was normal bilaterally with no evidence of papilledema. She scored a 26/38 on the Kokmen Short Test of Mental Status, scoring abnormally in the domains of attention, calculation, abstraction, information, and recall. Mrs. S was observed to have difficulty understanding complex commands and expressing herself. Motor strength was normal throughout. The patient was noted to have a tonically extended right great toe; the remainder of her muscle stretch reflexes were normal. She had no difficulty with rapid alternating movements. There were no fasciculations or tremor. The remainder of the physical examination was within normal limits.
Laboratory testing to rule out metabolic and systemic etiologies, including complete blood count, electrolytes, vitamin B12, liver enzymes, serum protein electrophoresis, and thyroid-stimulating hormone, were all within normal limits. A head computed tomography (CT) scan (Figure 1) revealed a 5.6 x 5.6 x 4.6–cm cystic structure in or adjacent to the left thalamus and basal ganglia. The structure was noted to exert mass effect on the midbrain with compression of the cerebral aqueduct leading to hydrocephalus, with enlargement of the lateral ventricles including the temporal horns and the third ventricle.
Subsequently, a magnetic resonance imaging (MRI) of the brain with and without intravenous contrast was performed (Figure 2). The study confirmed the presence of a round cystic mass centered in and expanding the posterior body of the left lateral ventricle. The lesion was seen to abut the left thalamus, left lentiform nucleus, septum pellucidum, and choroid plexus within the left atrium. The fluid within the cystic mass followed cerebrospinal fluid (CSF) contrast enhancement on all imaging sequences. Mass effect on the cerebral aqueduct, moderate ventriculomegaly, and a 1.6-cm focal subfalcine herniation to the right were visible.
Approximately two weeks after her initial presentation to her primary care provider, the patient’s neurosurgeon utilized an endoscopic approach through the left lateral ventricle to fenestrate the anterior wall of the cyst into the frontal horn of the lateral ventricle. The choroid plexus was visualized; it was large and had multiple small cysts associated with it. The choroid plexus was attached to the large cyst membrane. It was hoped that large fenestrations would be definitive treatment for the cyst. Histology confirmed the diagnosis of a choroid plexus cyst (CPC).
The choroid plexus lines the ventricles of the brain and produces CSF. A fold of the epithelial lining of the choroid plexus may be pinched off to form a cyst, most commonly in one of the lateral ventricles. They are commonly found on prenatal sonography and are associated with trisomy 18 of the fetus but usually resolve by 26-28 weeks.1 Most CPCs are small (less than 1 cm in diameter) and asymptomatic.2 A CPC may gradually increase in size and cause ventricular dilation or outflow obstruction of the CSF, most commonly at the foramen of Monro, leading to obstructive hydrocephalus.3 Symptomatic CPCs are most frequently found in children, especially in males.4 Large symptomatic CPCs in adults are extremely rare.5 Other than case reports of symptoms triggered by head trauma4,6 and a preponderance for the male sex,6 a review of the literature does not reveal any reported risk factors for the development of symptomatic CPCs.
Symptoms due to CPCs are typically related to the obstruction of CSF flow and ventricular enlargement. Headache is the most commonly reported symptom. Mental status changes, nausea, vomiting, gait disturbance, bradycardia, dizziness, decreased vision, unilateral motor and/or sensory involvement, seizures, and coma have all been described with CPCs. Episodic symptoms may be present if the cyst is pedunculated and has a ball-and-chain effect blocking the foramen of Monro.3-5,7,8
Imaging is the cornerstone of the evaluation, and typically reveals dilation of the lateral ventricles. Computed tomography reveals a focal enlargement of the trigone of the lateral ventricles with a well-defined mass of density similar to CSF. The cyst does not enhance and the enhancing choroid plexus is displaced.4 Magnetic resonance imaging is used to define the precise location of the cyst with a thin cyst wall visible next to the ventricular lining. The signaling corresponds to that of CSF on both T1- and T2-weighted images.9 Laboratory work-up is often unrevealing. The differential for cystic lesions in the ventricular system includes CPCs, colloid cysts, ependymal cysts, arachnoid cysts, epidermoid cysts, focal porencephaly, and cysticercosis.4 In the case of Mrs. S, the type of cyst was unknown before biopsy.
Histologically, CPCs have a fibrous outer membrane and an inner layer of cuboidal epithelial cells of the choroid plexus.4 Pathology specimens typically show reactivity for S-100 and markers of normal neuroepithelium, including transthyretin (prealbumin) and epithelial membrane antigen.10
There are no effective medical treatments described for CPCs. Most CPCs are small and asymptomatic and require only periodic observation. Surgical treatment to reduce the size of the cyst to allow normal CSF flow is indicated when obstructive symptoms are present.11 Among surgical options, endoscopic total removal of the cyst wall best prevents recurrence and minimizes invasive procedures.4,6 Other surgical options include endoscopic or open fenestration of the cyst into the ventricle, placement of a ventriculocystoperitoneal shunt, stereotactic evacuation of the cyst content, and surgical total or partial resection of the cyst.4,6 Post-fenestration prognosis is generally good regardless of the surgical approach.4
Several unique aspects of Mrs. S’s case deserve mention. She had a large symptomatic CPC, which is exceedingly rare in the adult population. In addition, Mrs. S presented with synchronous rapid decline of both cognitive function and gait. At the time of evaluation, Mrs. S’s cognitive symptoms included difficulty with recall, attention, and day-to-day activities suggestive of executive dysfunction. Her cognitive assessment supported these symptoms, revealing disturbance in multiple cognitive domains. This was suggestive of a dementing process. Among the differential diagnoses for cognitive impairment, relatively few etiologies would also lead to a focal unilateral gait disturbance. These include lesions affecting the frontal lobe, such as space-occupying lesions or hydrocephalus, and multi-infarct dementia.12-14 Normal-pressure hydrocephalus, Lewy body dementia with Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, vitamin B12 deficiency, intoxication with alcohol or sedative drugs, and neurosyphilis can also result in coexisting cognitive impairment and more global gait dysfunction.15 The American Academy of Neurology recommends that structural neuroimaging with noncontrast head CT or MRI be routine in the initial evaluation of patients with dementia.16 Because of the progressive nature and focal-aspect of Mrs. S’s symptoms, a space-occupying lesion was suspected. Her case illustrates key findings associated with cerebral lesions among older adults.
Outcome of the Case Patient
Mrs. S tolerated the endoscopic fenestration of the cyst well. On postoperative day 1, she was transferred to the neurosurgical floor and was able to tolerate a regular diet, progressively ambulate, and void spontaneously. Some immediate improvement in her gait was noted. Having no significant complications postoperatively, Mrs. S was discharged after two days. One week after the surgery, Mrs. S and her husband reported over the phone that she was doing very well. Her gait and memory had both improved dramatically.
At her three-week postoperative evaluation with neurosurgery, it was felt that there was a dramatic improvement in her neurological status. She was walking independently, and Mr. S reported that both her personality and mental clarity had returned to normal. At the time of this visit, a follow-up CT scan was performed (Figure 3). The cyst had decreased in size to 4.0 x 4.3 x 4.0 cm and produced a lesser mass effect on the cerebral aqueduct with reduction of the ventricular enlargement. There was a lesser amount of periventricular low-attenuation change, which was again attributed to transependymal flow of CSF.
Follow-up with her primary care physician nine months after the surgery revealed that Mrs. S continued to show a marked improvement in cognitive status, gait, and mood. She had started an exercise program and noted decreased problems with tripping and falls. She scored 34/38 on the Kokmen Short Test of Mental Status, losing points only for calculations and recall. Mrs. S agreed to return for evaluation if she experienced a recurrence of cognitive change or gait disturbance.
The authors report no relevant financial relationships.
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Ms. Sontag is a second-year medical school student at the Mayo Clinic College of Medicine, Rochester, MN, and Dr. Tung is from the Department of Internal Medicine, Division of Primary Care Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN.