**3. SIH and aseptic meningitis**

SIH is an important and relatively frequent cause of newly onset daily persistent posi‐ tional headaches in young and middle-aged individuals. Women are effected more fre‐ quently than men with a ratio of approximately 1.5/1. It is diagnosed about half as frequently as spontaneous subarachnoid hemorrhage and its incidence is estimated to be

Throbbing headache occurring or worsening in upright position and improving after lying down, so called "orthostatic headache", low CSF pressure, and diffuse pachymeningeal en‐ hancement on brain magnetic resonance imaging (MRI) are the major features of the classic

The clinical presentations and radiological findings may vary. Diagnosis is largely based on clinical suspicion, cranial MR findings and myelographic detection of dural leak. The posi‐ tional characteristics of the headache should always be questioned in patients admitting with meningeal irritation signs. Orthostatic headache, characteristic imaging features on MRI and instantaneous improvement of symptoms with a successful blood patch are key points of differential diagnosis from viral meningoencephalitis or other causes of aseptic

> **A. Diffuseand/or dull headache that worsens within 15 minutes after sittingor standing, fulfilling criterion D and with ≥ 1 of the following:**

1. Evidence of low CSF pressure on MRI (eg,pachymeningeal enhancement) 2. Evidence of CSF leakage on conventionalmyelography, CT myelography, or

3. CSF openingpressure <60 mm H2O in sitting position

According to the International Classification of Headache Disorders, 2nd Ed42 (4)

**C. No history ofdural puncture or other cause of CSF fistula**

**D. Headache resolves within 72 hours after epidural blood patching**

**Table 1.** Diagnostic Criteria for Headache Due to Spontaneous Spinal CSF Leak and Intracranial Hypotension

syndrome. Many other signs and symptoms may associate.

The diagnostic criteria used to verify the SIH cases are on shown on Table 1.

five per 100 000 [3].

34 Encephalitis

meningitis syndrome.

**2. Diagnostic criteria of SIH**

1. Neckstiffness 2. Tinnitus 3. Hypacusia 4. Photophobia 5. Nausea

cisternography

**B. At least1 of the following:**

Patients admitted with fever, headache and CSF findings revealing lymphocytic pleocytosis, elevated protein concentration and normal glucose levels are prone to be misdiagnosed as viral meningoencephalitis or usually aseptic meningitis [5].

The clinical presentation of aseptic meningitis is generally nonspecific, with fever, headache, nausea and vomiting, occasionally accompanied by photophobia and a stiff neck. Physical examination typically reveals signs of nuchal rigidity

The syndrome of "aseptic meningitis" including differing etiologies and disorders, presents a diagnostic challenge to the clinician [6]. Although many infectious and nonin‐ fectious etiologies exist for this syndrome, viruses, especially nonpolio enteroviruses, are the most common (>85%) and most important agents encountered. Although seasonal variation is relative and not absolute, enteroviruses are most likely to be the cause of aseptic meningitis occurring during the summer or fall. The onset of symptoms is char‐ acteristically abrupt and typically includes headache, fever, nausea or vomiting, malaise, photophobia, and meningismus.

Because the presenting signs and symptoms of enteroviral meningitis are not distinctive, tu‐ berculosis meningitis, herpes simplex encephalitis, HIV encephalitis and parameningeal in‐ fection that may mimic aseptic meningitis in their initial presentations must not be overlooked.

SIH may mimic aseptic meningitis. The main features of aseptic meningitis and SIH cases are compared in a case series newly reported form Turkey [7]. Various clinical and laborato‐ ry features of 11 consecutive cases of SIH and 10 consecutive cases of aseptic meningitis are given below (Table 2).

All of the 11 patients with SIH reported that their headache was occurring or worsening within minutes or hours assuming the upright position and improving by lying down, de‐ fined as "orthostatic headache". All met the diagnostic criteria defined by International Headache Society. The median duration of sudden-onset orthostatic headache was 10 days, ranging between 1 to 30 days. Five cases (5/11) had a previous diagnosis of migraine be‐ cause of chronic headache. The newly onset orthostatic headache was throbbing and diffuse in all cases distributing from posterior neck (5/11), from frontal area (4/11), from left tempo‐ ral region (1/11) and from left parietal region (1/11) to the whole cranium. The typical posi‐ tional characteristics of the headache were noticed with further questioning of the patients.

Hearing changes, disturbed sense of balance, and nausea were noted in all patients. Posteri‐ or neck pain and vomiting were described in 9, tinnitus in 3 patients, and echoing in 1 case.

Stiff neck was detected in 5 patients, and fever (axillary; >37.3°C) in 7 patients. The highest temperatures of those with fever were measured as follows; 38.7 <sup>o</sup> C, 38.3 <sup>o</sup> C, 38.1 <sup>o</sup> C, 38 <sup>o</sup> C, 38.9 oC, 38.2 oC and 38.5 oC.

Eight of 11 cases had visual changes as blurring (5/11) and diplopia (5/11).

Among neurological disorders photophobia (8/11), phonophobia (8/11) were most frequent followed by subtle cognitive deficits (5/11), amnesia (4/11), confusion & syncope (3/11), dys‐ geusia (3/11), facial numbness (2/11), convulsion, hyperexcitability, dysarthria, ataxia, facial weakness, facial spasm (each 1/11).

fuse severe encephalopathy with marked depression of consciousness, hyperexcitability

Spontaneous Intracranial Hypotension: What An Infectious Disease Physician Should Know?

http://dx.doi.org/10.5772/53744

37

A 40 year old female [8] was admitted to Stanford University School of Medicine in Califor‐ nia with a progressive cognitive decline of 2 to 4 weeks' duration. She developed a newly onset diffuse headache in orthostatic nature one month ago and she suffered a brief general‐ ized seizure 2 weeks before admission. Her computerized tomography (CT) scan and elec‐ troencephalography (EEG) were normal and she was diagnosed as SIH with diffuse pachymeningitis on MRI, low CSF opening pressure (60 mm/H2O) immediate clinical im‐

Two similar cases with SIH, with no defined preexisting comorbidities and newly pre-diag‐ nosed as meningoencephalitis, were reported from Istanbul-Turkey. Both were young (29 and 21 years) males, brought to emergency departments of different hospitals in coma with a 3-year of time interval. One had a generalized tonic-clonic convulsion and the other who was evaluated as nonconvulsive status had hyperexcitability. Antiepileptic agents were ad‐ ministered for both before admission to the university hospital where the final diagnosis

The first diagnostic steps for these cases were aimed to exclude Herpes encephalitis due to its high frequency and being a medical emergency. Although the patients were admitted with im‐ paired conscious and convulsions, there were no signs of contrast enhancement (e.g. temporal, parietal or frontal lobe) suggesting HSV 1 involvement, the CSF opening pressures were slight‐

The diagnosis of SIH was established on the basis of specific cranial MR images, negative

The most common cause of non-epidemic (not affecting a large number of people at once) encephalitis in developed countries is the herpes simplex virus. The most common signs of acute viral encephalitis are fever, headache, and a change in level of conscious‐ ness. Other common signs are the eyes becoming sensitive to light (photophobia), confu‐

Some people exposed to insect-borne encephalitis viruses do not develop symptoms of ence‐ phalitis. They may only experience low-grade fever, drowsiness, and flu-like symptoms of malaise (general feeling of illness) and myalgia (muscle aches). Headache, vomiting, and sensitivity to light may follow. The epidemiological relatedness and a history of a travel, re‐

Symptoms and signs of meningeal irritation (photophobia and nuchal rigidity) are usually absent with a pure encephalitis but often accompany a meningoencephalitis. Patients with encephalitis have an altered mental status ranging from subtle deficits to complete unre‐ sponsiveness. Seizures are common with encephalitis, and focal neurologic abnormalities can occur, including hemiparesis, cranial nerve palsies, and exaggerated deep tendon and/or

ly low (60 and 90 mmH2O consequently) and HSV 1 PCR results were negative.

CSF findings and the prompt response to blood patch within 72 hours.

call of an insect exposure are useful to exclude this type of encephalitis.

pathologic reflexes. Patients may appear confused, agitated, or obtunded.

provement responding to placement of epidural blood patch.

or convulsion [7,8].

was established.

sion, and sometimes seizures.


SIH: Spontaneous intracranial hypotension, CSF: Cerebrospinal fluid, NR: normal range, PCR: polymerase chain reac‐ tion, HSV: Herpes simplex virus, TB: tuberculosis

\* Only five were measured.

\*\* Pleocytosis was detected in only four SIH cases while all (n=10) cases of aseptic meningitis had lymphocytic pleocy‐ tosis varying between 32 and 1340 /mm3.

\*\*\* Four SIH and seven aseptic meningitis cases had elevated CSF protein levels.

**Table 2.** Comparison of SIH and Aseptic Meningitis Cases

### **4. SIH and encephalitis**

Despite the benign character of SIH, some rare cases may present with severe neurologi‐ cal findings. A few cases of SIH are reported whose chief clinical manifestation were dif‐ fuse severe encephalopathy with marked depression of consciousness, hyperexcitability or convulsion [7,8].

Among neurological disorders photophobia (8/11), phonophobia (8/11) were most frequent followed by subtle cognitive deficits (5/11), amnesia (4/11), confusion & syncope (3/11), dys‐ geusia (3/11), facial numbness (2/11), convulsion, hyperexcitability, dysarthria, ataxia, facial

**CSF FINDINGS (Mean±SD)**

**CSF Glucose /blood glucose (mg/dl) (NR: 40-80)**

61± 12/102 ±21

> 63±11/ 114±13

**Enterovirus PCR positivity**

**HSV PCR positivity**

0/11 0/10 0/10

2/10 0/10 0/10

**TB PCR positivity**

weakness, facial spasm (each 1/11).

**CLINICAL SIGNS & SYMPTOMS**

**Headache**

SIH (n=11)

36 Encephalitis

Aseptic Meningitis (n=10)

**Fever**

**Nausea – Vomiting**

tion, HSV: Herpes simplex virus, TB: tuberculosis

**Table 2.** Comparison of SIH and Aseptic Meningitis Cases

tosis varying between 32 and 1340 /mm3.

**4. SIH and encephalitis**

\* Only five were measured.

**Stiff Neck**

**Opening pressure**

**(mmH**

11/11 7/11 10/11 5/11 59 ±16.4 229±200 76 ± 5 55±49

10/10 6/10 6/10 5/10 160±28.4 360±50 84±13 93±92

\*\*\* Four SIH and seven aseptic meningitis cases had elevated CSF protein levels.

**2**

**Leukocyte (/ mm3) (NR:0-5)\*\***

**Lympho-cyte (/mm3) (NR:0-5)**

SIH: Spontaneous intracranial hypotension, CSF: Cerebrospinal fluid, NR: normal range, PCR: polymerase chain reac‐

\*\* Pleocytosis was detected in only four SIH cases while all (n=10) cases of aseptic meningitis had lymphocytic pleocy‐

Despite the benign character of SIH, some rare cases may present with severe neurologi‐ cal findings. A few cases of SIH are reported whose chief clinical manifestation were dif‐

**Protein concentra-tion (mg/dl) (NR:15-45) \*\*\***

**O) (NR: 50-180)\***

A 40 year old female [8] was admitted to Stanford University School of Medicine in Califor‐ nia with a progressive cognitive decline of 2 to 4 weeks' duration. She developed a newly onset diffuse headache in orthostatic nature one month ago and she suffered a brief general‐ ized seizure 2 weeks before admission. Her computerized tomography (CT) scan and elec‐ troencephalography (EEG) were normal and she was diagnosed as SIH with diffuse pachymeningitis on MRI, low CSF opening pressure (60 mm/H2O) immediate clinical im‐ provement responding to placement of epidural blood patch.

Two similar cases with SIH, with no defined preexisting comorbidities and newly pre-diag‐ nosed as meningoencephalitis, were reported from Istanbul-Turkey. Both were young (29 and 21 years) males, brought to emergency departments of different hospitals in coma with a 3-year of time interval. One had a generalized tonic-clonic convulsion and the other who was evaluated as nonconvulsive status had hyperexcitability. Antiepileptic agents were ad‐ ministered for both before admission to the university hospital where the final diagnosis was established.

The first diagnostic steps for these cases were aimed to exclude Herpes encephalitis due to its high frequency and being a medical emergency. Although the patients were admitted with im‐ paired conscious and convulsions, there were no signs of contrast enhancement (e.g. temporal, parietal or frontal lobe) suggesting HSV 1 involvement, the CSF opening pressures were slight‐ ly low (60 and 90 mmH2O consequently) and HSV 1 PCR results were negative.

The diagnosis of SIH was established on the basis of specific cranial MR images, negative CSF findings and the prompt response to blood patch within 72 hours.

The most common cause of non-epidemic (not affecting a large number of people at once) encephalitis in developed countries is the herpes simplex virus. The most common signs of acute viral encephalitis are fever, headache, and a change in level of conscious‐ ness. Other common signs are the eyes becoming sensitive to light (photophobia), confu‐ sion, and sometimes seizures.

Some people exposed to insect-borne encephalitis viruses do not develop symptoms of ence‐ phalitis. They may only experience low-grade fever, drowsiness, and flu-like symptoms of malaise (general feeling of illness) and myalgia (muscle aches). Headache, vomiting, and sensitivity to light may follow. The epidemiological relatedness and a history of a travel, re‐ call of an insect exposure are useful to exclude this type of encephalitis.

Symptoms and signs of meningeal irritation (photophobia and nuchal rigidity) are usually absent with a pure encephalitis but often accompany a meningoencephalitis. Patients with encephalitis have an altered mental status ranging from subtle deficits to complete unre‐ sponsiveness. Seizures are common with encephalitis, and focal neurologic abnormalities can occur, including hemiparesis, cranial nerve palsies, and exaggerated deep tendon and/or pathologic reflexes. Patients may appear confused, agitated, or obtunded.

Results of imaging in patients with encephalitis may or may not demonstrate abnormal ra‐ diographic findings on CT or MRI modalities. CT scanning is useful to rule space-occupying lesions or brain abscess. MRI is sensitive for detecting demyelination, which may be seen in other clinical states presenting with mental status changes (eg. progressive multifocal leu‐ koencephalopathy) and typical contrast enhancing (mostly temporal lesions).

spread and increasing use of MRI, SIH is more frequently recognized in recent years as an important cause of new onset persistent, daily, positional headaches. Diffuse pachy‐ meningeal (dural) contrast enhancement is the main feature on cranial MRI. Some other findings of SIH have been described: Enlargement of pituitary, tenting of the optic chiasm, subdural fluid collections, engorged cerebral venous sinuses and findings due to sagging of the brain such as obliteration of subarachnoid cisterns, crowding of posterior

Spontaneous Intracranial Hypotension: What An Infectious Disease Physician Should Know?

http://dx.doi.org/10.5772/53744

39

**Figure 1.** Thickening in meninges demonstrating pachymeningeal contrast enhancement (arrows) and enlargement of the pituitary gland (arrowhead)in a 36 years old female patient [7], presenting with orthostatic headache, stiff neck and fever. **b.** Axial FLAIR image of the same case showing bilateral thin subdural collection (arrow). **c.** Findings of sag‐ ging brain (arrow) in a 37 year old female (case 1] presenting with fever, severe headache, nausea and vomiting. **d.** Engorgement in cerebral veins (arrows) of a 44 year old male presenting with fever and meningeal irritation signs

]. *(Derived from ref. 7. Photo courtesy of Sait Albayram,*

whose LP revealed a marked lymphocytic pleocytosis[450 / mm3

*with permission)*

fossa and descent of cerebellar tonsils [5].

Initial examination of the CSF, although not diagnostic, will usually confirm the presence of inflammatory disease of the CNS. The findings with encephalitis, aseptic meningitis and me‐ ningoencephalitis are generally indistinguishable.
