Skip to main content
main-content
Erschienen in: BMC Infectious Diseases 1/2022

Open Access 04.03.2022 | COVID-19 | Case report

Normal pressure hydrocephalus associated with COVID-19 infection: a case report

verfasst von: Thaís de Maria Frota Vasconcelos, Paulo Ribeiro Nóbrega, Glauber de Menezes Ferreira, Moysés Loiola Ponte de Souza, Alander Sobreira Vanderlei, José Daniel Vieira de Castro, Pedro Braga-Neto, Manoel Alves Sobreira-Neto

Erschienen in: BMC Infectious Diseases | Ausgabe 1/2022

Abstract

Background

COVID-19 is a pandemic disease responsible for many deaths worldwide. Many neurological manifestations have been described. We report a case of normal pressure hydrocephalus (NPH) 2 months after acute COVID19 infection, in a patient without other risk factors.

Case presentation

A 45-year-old male patient presented an 8-month history of progressive gait disorder and cognitive impairment after being hospitalized for SARS-CoV-2 infection. Magnetic resonance imaging (MRI) was compatible with NPH. A spinal tap test was positive and there was progressive improvement after shunting, with complete resolution of symptoms.

Conclusion

Other infections such as syphilis, cryptococcosis and Lyme disease have been associated with NPH. Possible mechanisms for NPH after COVID include disruption of choroid plexus cells by direct viral invasion or as a result of neuroinflammation and cytokine release and hypercoagulability leading to venous congestion and abnormalities of CSF flow. Given the significance of NPH as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19 and understand the mechanisms behind this association.
Hinweise
Thaís de Maria Frota Vasconcelos and Paulo Ribeiro Nóbrega contributed equally to this work

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Abkürzungen
ACE2
Angiotensin converting enzyme 2
CNS
Central nervous system
ICP
Intracranial pressure
MRI
Magnetic resonance imaging
NPH
Normal pressure hydrocephalus
SAH
Subarachnoid hemorrhage
TBI
Traumatic brain injury

Background

COVID-19 is a pandemic disease caused by an RNA virus named SARS-CoV-2 and is primarily a respiratory disease involving lower and upper airways, although many neurologic manifestations have been described [1]. Similarly, to what has been reported with other coronaviruses, such as MERS-CoV and SARS-CoV-1, this pathogen has shown possibly neurotropic and neuroinvasive properties resulting in a wide range of neurologic manifestations [1].
Normal pressure hydrocephalus (NPH) is a condition characterized by a triad of cardinal symptoms composed by gait disorder, urinary incontinence and cognitive decline associated with dilated ventricles, in the absence of intracranial hypertension [2].
Herein, we report a case of Normal Pressure Hydrocephalus occurring two months after acute COVID19 infection.

Case presentation

A 45-year-old man presented with a history of imbalance and progressive gait disorder for the last 8 months, associated with memory impairment. He had a previous history of bipolar disorder and type II diabetes mellitus and reported a COVID19 infection 2 months before initial presentation of neurologic symptoms.
Initial symptoms of SARS-Cov-2 infection were fever, anosmia, dysgeusia and anorexia. A real-time reverse-transcriptase-polymerase-chain-reaction assay (Allplex™ SARS-CoV-2 Assay—N/RdRP/S genes) confirmed the diagnosis. Hospitalization for seven days and oxygen via nasal cannula were necessary. At discharge, he was able to walk unassisted.
Two months after acute COVID19 infection the patient started a progressive gait disorder, complaining that he felt like his feet were glued to the ground. After a few weeks, he started forgetting recent facts and his family complained of excessive daytime sleepiness and blunted affect. He progressed to executive dysfunction and difficulty in performing his labor activities. There was no history of head trauma, subarachnoid hemorrhage (SAH) or meningitis. There was also no family history of neurologic diseases.
Neurologic examination revealed short-term memory loss, slow processing speed, inattention, difficulty in planning and executive dysfunction. A mild tetraparesis was also perceived, with brisk deep tendon reflexes in four limbs. There was no clonus and flexor plantar responses were observed. There was mild rigidity of the upper limbs, without cogwheeling. Gait was slow and magnetic, with short steps, feet close to the ground and postural instability.
Laboratory evaluation did not reveal any abnormalities (Table 1). Complete blood count, renal function, liver enzymes and thyroid hormones were normal. Serology was negative for Syphilis and HIV. Vitamin B12 levels were also normal.
Table 1
Laboratory and cerebrospinal fluid analysis in a patient with normal pressure hydrocephalus after COVID19
Variables
COVID symptoms onset
Neurological symptoms onset
Reference values
Serum tests
   
 Hemoglobin (g/dL)
15.9
14.5
13–17.5
 Leukocytes (cells/mm3)
7640
5600
4000–11,000
 Lymphocytes (cells/mm3)
770
2420
1000–3500
 Platelets (number/mm3)
259.000
255.000
150,000–450,000
C-reative protein (mg/dL)
6.37
< 0.3
 ESR (mm/h)
27
 
 D-Dimer (ng/mL)
300
 
< 600
 Sodium (mMol/L)
142
136–146
Potassium (mMol/L)
4,3
3.5–5.1
 Calcium (mg/dL)
9,3
1.16–1.32
 Magnesium (mg/dL)
2,3
1.6–2.6
 Blood urea nitrogen (mg/dL)
21
14
7–20
 Creatinine (mg/dL)
1.1
0.92
0.5–1.3
 AST (U/L)
39
  
 ALT (U/L)
49
  
 TSH (µlU/mL)
1542
0.550–4.780
 HIV I, II
Negative
Negative
 Syphilis
Negative
Negative
Analysis of cerebrospinal fluid
   
 Cell count (cells/mm3)
2
0–4
 Differential cell count
100% lymphocytes
 Protein (mg/dL)
26
15–45
 Glucose (mg/dL)
74
 VDRL
Negative
Negative
 Gram stain
Negative
Negative
 Fungal stain (India-ink)
Negative
Negative
PT prothrombin time; aPTT activated partial thromboplastin time; VDRL Venereal Disease Research Laboratory; PCR polymerase chain reaction
Brain magnetic resonance imaging (MRI) disclosed moderately dilated supratentorial ventricular system with callosal angle reduction and aqueduct flow-void (Fig. 1). A high-volume (40 ml) lumbar tap test was performed and revealed an opening pressure of 100mmH2O (normal range < 200 mmH2O). There was marked improvement of gait and balance after the procedure—10 m timed up and go (TUG) before the procedure of 18.4 s (32 steps) and after the procedure of 16.7 s (27 steps). CSF analysis was entirely normal (Table 1).
A diagnosis of Normal Pressure Hydrocephalus was made and a ventriculoperitoneal shunt was placed without adverse events. Thirty days later there was significant improvement of gait, now presenting normal speed and step length. Cognitive functions also improved substantially, and he returned to his previous work activities. The patient reports that his ability to perform his labor activities is normal and is very pleased with his clinical outcome.

Discussion and conclusion

We have described a previously healthy patient who developed NPH two months after COVID19 infection, presenting with gait apraxia and cognitive impairment.
Normal pressure hydrocephalus has been classified as idiopathic or secondary [3]. Many diseases have been implicated in its etiology, such as subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), meningitis, stroke and intracranial neoplasms [3]. Some specific infectious diseases have also been reported as possible etiologies for NPH, including Lyme disease, neurosyphilis and cryptococcosis [4]. There are reports of hydrocephalus following SAH in patients with concomitant coronavirus infections [5, 6], but as far as we know this is the first case of NPH associated with COVID-19 infection without preceding SAH or stroke.
The main theory to explain central nervous system (CNS) invasion is that SARS-CoV-2 probably enters olfactory nerves through interaction of the viral S protein with the Angiotensin Converting Enzyme 2 (ACE2) receptor on olfactory epithelium [1]. The spatial distribution of ACE2 receptors in the CNS was studied using brain transcriptome data banks and high concentrations of these receptors were found in the choroid plexus of lateral ventricles suggesting that the choroid plexus could be a pathway for SARS-CoV-2 to enter the CNS [7]. It is possible that this interaction between the virus and the choroid plexus could alter the dynamics of CSF flow, contributing to NPH. An animal model study of hydrocephalus after SAH has demonstrated that inflammation of choroid plexus cells marked by increase in NF-kB results in dysfunction of these barrier cells leading to production of increased abnormal protein-rich CSF, and consequentially in hydrocephalus due to excess CSF production [8].
Many neuroinvasive viruses such influenza A and B can initially trigger an innate immune response by activating microglia [9]. Microglia also activate astrocytes that can modulate the recruitment and activation of additional microglial and other immunocompetent cells [10]. Microglial and astrocyte activation as well as massive cytokine release might lead to inflammation of arachnoid villi resulting in fibrosis and adhesion of these structures, reduction in CSF reabsorption, and consequently to hydrocephalus [11]. Another possible factor in the etiology of COVID19-associated NPH is a hypercoagulable state induced by the systemic response to SARS-CoV-2 [12], which could lead to venous congestion and CSF flow abnormalities [11].
In a series of patients with persistent headache after COVID-19 infection 84.6% had increased intracranial pressure (ICP) in the absence of meningitis [13]. It is possible that some of these patients with initially elevated ICP might progress to NPH over time as the CSF compartment rearranges itself in a larger volume to maintain physiologic ICP according to Laplace’s law [14].
Unfortunately, we were not able to test CSF for COVID antibodies due to local technical limitations. In a recent study of 8 patients with COVID-associated encephalopathy (ref [1]) all patients had positive anti-SARS-CoV-2 antibodies in CSF, but only 4 of them (50%) had high titers comparable to blood titers. Among these 4 patients, only 1 had intrathecal anti-SARS-CoV-2 IgG synthesis, the remainder had disruption of the blood–brain-barrier. As such, it is still unclear whether specific anti-SARS-CoV-2 antibodies play a role in neurologic manifestations associated with COVID, or if blood–brain-barrier dysfunction with cytokine influx is the main component in such manifestations [15].
We have described the first case of normal pressure hydrocephalus possibly associated with COVID19 infection. Although pathophysiological mechanisms are still unclear and we cannot be certain that NPH occurred because of COVID19, there was a clear temporal correlation, and the patient did not have other risk factors for NPH. Given the significance of this condition as a cause of reversible dementia, it is important to consider the possibility of a causal association with COVID19. More reports are necessary to confirm this association and clarify its mechanisms.

Acknowledgements

Not applicable.

Declarations

Not applicable.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Competing interests

On behalf of all authors, the corresponding author states that there is no conflict of interest.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Literatur
6.
Zurück zum Zitat Weisbrod L, Davidson C, Gard A, Surdell D. Low-pressure hydrocephalus in spontaneous angiogram-negative subarachnoid hemorrhage following COVID-19 infection. Cureus. 2021;13:7. Weisbrod L, Davidson C, Gard A, Surdell D. Low-pressure hydrocephalus in spontaneous angiogram-negative subarachnoid hemorrhage following COVID-19 infection. Cureus. 2021;13:7.
Metadaten
Titel
Normal pressure hydrocephalus associated with COVID-19 infection: a case report
verfasst von
Thaís de Maria Frota Vasconcelos
Paulo Ribeiro Nóbrega
Glauber de Menezes Ferreira
Moysés Loiola Ponte de Souza
Alander Sobreira Vanderlei
José Daniel Vieira de Castro
Pedro Braga-Neto
Manoel Alves Sobreira-Neto
Publikationsdatum
04.03.2022
Verlag
BioMed Central
Erschienen in
BMC Infectious Diseases / Ausgabe 1/2022
Elektronische ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-022-07184-x

Weitere Artikel der Ausgabe 1/2022

BMC Infectious Diseases 1/2022 Zur Ausgabe

Corona-Update

Die aktuelle Entwicklung im Überblick: Nachrichten, Webinare, Übersichtsarbeiten.

Passend zum Thema

Neue Wege in der digitalen Diagnostik

Ein Frühsymptom der Alzheimer-Erkrankung können leichte kognitive Störungen sein. Um diese zu erkennen, können Ärzt:innen nun auf neotivCare setzen: Gedächtnistests liefern bereits früh im Krankheitsverlauf belastbare Befunde und lassen so eine medizinische Bewertung von Gedächtnisproblemen zu.

Je früher, desto besser, Alzheimer-Früherkennung

Leichter gesagt als getan – in der Praxis ist die Frühdiagnose von leichten kognitiven Einschränkungen (sog. Mild cognitive impairment, MCI) oder der Alzheimer-Krankheit aus vielen Gründen eine Herausforderung. Wieso sich Früherkennung aber lohnt, erfahren Sie hier.

ANZEIGE

Neuroscience News: Wissenswertes zu Alzheimer, MS, NMOSD und SMA

Der Neuroscience Content Hub von Roche informiert über die neurodegenerativen Erkrankungen Alzheimer, Multiple Sklerose, Neuromyelitis-optica-Spektrum-Erkrankungen und Spinale Muskelatrophie. Entdecken Sie Wissenswertes zu Therapieoptionen, aktuelle Kongress-News und hören Sie Expertenstimmen aus der Praxis.

Passend zum Thema

ANZEIGE

Fragen und Antworten zur COVID-19-Impfung

In diesem Beitrag finden Sie Antworten auf häufig gestellte Fragen zu den Coronaimpfungen. Beantwortet von Prof. Dr. med. Ulrich Heininger, Basel.

ANZEIGE

Dysphagie Screening Tool Geriatrie (DSTG)

Ende 2019 ist das neue Dysphagie Screening Tool Geriatrie (DSTG) der AG Dysphagie der Deutschen Gesellschaft für Geriatrie (DGG) erschienen.

ANZEIGE

consilium – Expertenwissen zu Themen aus dem Praxisalltag der Allgemeinmedizin und der Geriatrie

Das consilium Allgemeinmedizin/Geriatrie von InfectoPharm vermittelt Ihnen Expertenwissen zu Themen aus Ihrer alltäglichen Praxis. Dabei geht es in der Regel um aktuelle spannende Patientenfälle, relevante Therapiefragen oder Fragen zu geeigneten diagnostischen Maßnahmen sowie möglichen Differenzialdiagnosen. Machen Sie sich selbst ein Bild!