Abstract
While the cause of altered mentation in the elderly may be multifactorial, infectious etiologies may be missed. This case report aims to detail an account of a patient with dementia, found to have Lyme meningitis in the setting of a normal pressure hydrocephalus (NPH). The patient smelled of urine and presented with ambulatory dysfunction, fitting the “wet, wacky, and wobbly” triad of NPH while also having subjective chills and leukocytosis. Non-contrast brain CT scan showed dilated ventricles. Cerebrospinal fluid (CSF) studies suggested aseptic meningitis. Serum studies using a modified two-tiered algorithm confirmed the diagnosis of Lyme disease. Treatment of the underlying condition with a prolonged course of doxycycline improved symptoms and clinical course. Review of the literature on the association between Lyme meningitis and NPH reveals that few cases of Lyme-related NPH have been reported worldwide and further research into the pathophysiology, diagnostic approach, treatment modalities, and management of NPH secondary to Lyme meningitis may be warranted.
The differential diagnosis for an elderly male with altered mental status is broad. This case report describes normal pressure hydrocephalus (NPH) secondary to Lyme meningitis in an elderly patient living in an area endemic to Lyme disease. Lyme disease can manifest in many different ways, and as a result, the diagnosis can be difficult to make if not suspected. Rarely will Lyme disease progress to meningitis or NPH. Thus far, seven cases of NPH secondary to Lyme disease have been reported;1-7 although, this is the first from Pennsylvania. Lyme disease is estimated to be significantly underdiagnosed,4 and its incidence is continuing to increase.8 For these reasons, it is prudent for clinicians to have a low threshold for testing Lyme serology in cases of otherwise unexplained NPH. This case also warrants further research into both the risk of NPH in the setting of Lyme meningitis and an optimal treatment regimen.
Case Report
A male patient, aged 80 years, with a past medical history significant only for the presence of a pacemaker, presented to the emergency department (ED) of a community hospital in Pennsylvania (PA), USA during the summertime. He was brought from his assisted living home by family members who were concerned about his increasing weakness and confusion since suffering legal and financial issues with a family member. He was seen and evaluated by the admitting hospitalist 2 hours later.
His daughter reported the patient had been having several days of nausea with decreased appetite, generalized malaise, fatigue, and weakness. Notably, the patient also had subjective fevers but was afebrile on arrival. The daughter stated the patient was having difficulties with activities of daily living (ADLs) and instrumental activities of daily living (IADLs). The patient himself appeared confused and was able only to provide simple yes or no answers to direct questions. The patient responded “yes” when asked about urinary incontinence, difficulty walking, and loss of memory. He responded “no” to having symptoms of chest pain, palpitations, headaches, lightheadedness, shortness of breath, nausea, vomiting, diarrhea, or constipation.
On physical examination, the patient smelled of urine. The patient had no signs of trauma, and was normocephalic with a supple neck and no abnormalities on cardiovascular, pulmonary, abdominal, integumentary, and musculoskeletal examination. He had no focal neurologic deficits, but he was confused with tangential speech and oriented only to person.
Blood tests collected in the ED revealed: glucose 125 mg/dL (normal reference: 70-100 mg/dL fasting, <140 mg/dL random/non-fasting), white blood cell count (WBC) 14.33 K/uL (normal reference: 4.5-11 K/uL), thyroid stimulating hormone (TSH) 0.42 uIU/mL (normal reference: 0.4-4.0 uIU/mL), free T4 1.01 ng/dL (normal reference: 0.9-1.7 ng/dL), Vitamin B12 158 pg/mL (normal reference: 200-900 pg/mL), folate 11.8 ng/mL (normal reference: 2.7-17.0 ng/mL), and rapid plasma reagin (RPR) serology non-reactive (although fluorescent treponemal antibody-absorption was not performed). The patient is HIV negative. His electrocardiogram showed normal ventricular pacing; his chest radiograph showed his pacemaker with no abnormal cardiopulmonary findings. His brain computed tomography (CT) (Figure 1) showed dilation of the ventricles out of proportion to the size of the convexity sulci. The Evans’ index on CT was 0.45. Other radiographic features of NPH, such as enlarged temporal horns, periventricular hypodensities, a disproportionate enlargement of the subarachnoid space hydrocephalus (DESH), or a callosal angle < 900 was not noted. On day 2 of hospitalization, interventional radiology (IR) was therefore consulted along with neurosurgery to evaluate for lumbar puncture (LP).
Non-contrast brain CT showing dilated ventricles.
The next day, treatment for NPH by LP relieved his symptoms. Roughly 25 mL of CSF was removed on LP. The CSF was found to have 86 RBC/mm3 (normal reference: 0-5 RBC/mm3), 2 WBC/mm3 (normal reference: 0-5 WBC/mm3), 78 mg/dL glucose (normal reference: 50.4-75.6 mg/dL), and 56 mg/dL protein (normal reference: 15-45 mg/dL). The presence of 86 RBC/mm3 was likely secondary to a traumatic LP. Fungal and tubercular testing were not performed on the CSF. The opening pressure was 15 cm H2O (normal reference: 6-25 cm H2O)9. On serum studies (collected on the day of admission, resulting on day 4 of hospitalization), Lyme screen was equivocal for IgM, negative for IgG, and confirmatory Western Blot was positive for Lyme IgM (23KD and 39KD antibodies). The patient was subsequently diagnosed with aseptic meningitis secondary to Lyme and started on doxycycline 100 mg intravenously (IV) twice daily for 21 days (this antibiotic course was eventually transitioned to oral dosing once stable enough to be discharged). The patient was not a candidate for a ventriculoperitoneal shunt because of his acute infection. However, as his mentation, orientation, and conversation improved without degradation after the lumbar puncture and treatment of his Lyme disease, thyroid disease, and B12 deficiency, this did not impair recovery (Figure 2). The improvement in cognition may be due to treatment for vitamin B12 deficiency. Dementia did not completely resolve, likely due to primary dementia or other condition.
Approximate timeline of Lyme presentation, with symptoms of chills resolved in ED, consciousness improved after LP, and weakness improving after physical therapy. Note that dementia did not completely resolve, likely due to primary dementia or other condition.
Discussion
Differentiating between primary NPH and NPH secondary to other etiologies such as meningitis or neoplasm is important to direct management. Meningitis as an etiology for secondary NPH typically leads one to suspect infection, whether bacterial or aseptic - viral, Lyme, or Cryptococcal meningitis among those studied;10 however, there have been reported cases of autoimmune causes of meningitis such as rheumatoid).11 In the case of our patient, infectious meningitis was suspected due to this patient reportedly having had fevers and leukocytosis. Additionally, Lyme disease is among the most common reportable infections in Pennsylvania, with the Department of Health estimating 100,000 cases a year.12 Therefore, Lyme meningitis was moderately suspected on initial evaluation, both from an epidemiological as well as a clinical perspective. Lyme disease, caused by the Borrelia bacterium spread by the Ixodes tick, can present with multiple complications, including arthritis, heart rhythm defects, facial nerve palsy, impaired memory, and meningitis.13 Hence, Lyme disease should be considered as part of the differential etiology of meningitis.14 While neurological complications can present in up to 15% of patients with Lyme disease,15 only 6% of Lyme cases progress to meningitis.16
The events described in this case presentation occurred in 2021. Between September 2022 to December 2022, publications from 1990 to 2022 from PubMed were searched and evaluated for relevance and educational utility. The selection criteria were that the study must (1) discuss at length an incidence of Lyme disease or neuroborreliosis and (2) include an associated normal pressure hydrocephalus. Among cases of Lyme disease, seven have been reported with NPH, the last documented in 2009 (published in 2020).7 If untreated, Lyme poses the risk of the pathophysiologic progression to late stage neuroborreliosis.
Diagnostic methods in patients with suspected Lyme depend on the staging of Lyme disease. Serologic testing with a tiered algorithm is warranted in patients with late Lyme disease, or in this case, neurological manifestations. The two primary options for serologic testing include the traditional algorithm (initial enzyme immunoassay or immunofluorescence assay followed by a Western blot) or a modified algorithm. In our study, a modified two-tiered algorithm (with initial equivocal IgM serology and confirmatory Western Blot on the 23KD and 39KD Lyme IgM antibodies) was favored over the traditional algorithm because of the improved sensitivity, although modified algorithms were developed to better the sensitivity and specificity of early-stage Lyme disease.17 Other possible methods such as polymerase chain reaction (PCR) were considered, although Western blotting for IgG and IgM is generally a cheaper alternative.
Of note, RPR serologies were negative. A negative RPR or venereal disease research laboratory (VDRL) does not mean this patient was negative for syphilis, as titers can decrease with time and may even be negative in neurosyphilis cases. Finding a positive treponemal test in this patient and subsequent treatment for neurosyphilis would be recommended considering that Lyme serology and VDRL may cross-react.18
NPH is caused by enlargement of the lateral cerebral ventricles and distortion of corona radiata fibers, typically manifesting as the textbook “Wet, Wacky, and Wobbly” triad of urinary incontinence, dementia, and ambulatory dysfunction or gait disturbance.19 Diagnosis of NPH is made on imaging, either with a head CT or magnetic resonance imaging (MRI). Due to the nature of magnetic resonance, an MRI may be preferred to evaluate for any soft tissue mass such as a benign neoplasm or malignancy; however, an MRI in our patient was deferred, as the CT of the head already provided a diagnosis of NPH, which responded well to LP, and any additional follow-up MRI would not have significantly changed our management, given that this patient would be on a prolonged course of antibiotics regardless.
In addition to procedural therapy providing symptomatic relief, treating the underlying cause of NPH is paramount to patient outcomes. Treatment of Lyme meningitis requires a prolonged course of antibiotic therapy, typically using doxycycline or ceftriaxone. The adult dose of doxycycline is 100 mg orally twice daily for 14 to 21 days, although most healthcare providers will favor a longer course of antibiotics depending on severity.20 In this case, a course of IV doxycycline was administered while inpatient due to clinical severity, with transition to oral on discharge.
Conclusion
Healthcare providers treating patients with NPH should consider Lyme disease as a differential diagnosis because of the multiple reported cases of NPH secondary to Lyme disease. This case of meningitis and hydrocephalus provides an additional data point for Lyme-related NPH. Review of the literature demonstrates limited research in this area. Further studies into the pathophysiology, diagnostic approach, treatment modalities, and management of a patient with NPH secondary to Lyme meningitis may be of benefit for future cases of this disease process.
Footnotes
Sources of support: In compliance with ICMJE disclosure, all authors declare no conflicts of interest. All authors have declared that no financial support was received from any organization for the submitted work. All authors have declared that they have no financial relationships (or financial support in the form of grants, equipment, drugs, or any other sources) at present or in the past with any organizations that might have an interest in the submitted work. All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
- Received February 2, 2023.
- Revision received November 25, 2023.
- Accepted December 11, 2023.
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