Clinical Aspects in Which Symptoms May Indicate Cerebrospinal Fluid (CSF) Analysis

Abstract

This chapter aims to describe clinical aspects in which examination of cerebrospinal fluid is essential for diagnosis. Clinical signs and symptoms that may indicate analysis of cerebrospinal fluid may include changes in mental status, severe headache, difficulty speaking, difficulty walking, dizziness, fever, muscle weakness, sensitivity to light, and seizures. Cerebrospinal fluid is frequently collected by lumbar puncture—a procedure of mainly diagnostic value. Examination of the cerebrospinal fluid determines the appearance, chemical and cytological composition, and pressure. In some conditions, analysis of cerebrospinal fluid is no longer necessary to establish the diagnosis, but the presence of changes in cerebrospinal fluid increases the level of “comfort” for diagnosis. Today, the lumbar puncture is no longer used to examine all types of central nervous system disorders. However, it is still used to diagnose central nervous system infections, neuro-immunological disorders, tumours, Guillain-Barré syndrome, and multiple sclerosis.

1. Introduction

This chapter aims to describe clinical aspects in which examination of cerebrospinal fluid is essential for diagnosis.

Clinical signs and symptoms that may indicate analysis of cerebrospinal fluid may include changes in mental status, severe headache, difficulty speaking, difficulty walking, dizziness, fever, muscle weakness, sensitivity to light, and seizures.

Cerebrospinal fluid is frequently collected by a lumbar puncture—a procedure of mainly diagnostic value.

Examination of the cerebrospinal fluid determines the appearance, chemical and cytological composition, and pressure.

In some conditions, analysis of cerebrospinal fluid is no longer necessary to establish the diagnosis, but the presence of changes in cerebrospinal fluid increases the level of “comfort” for diagnosis.

CSF examination is important for the differential diagnosis of a range of central nervous system (CNS) infections, meningitis, encephalitis, as well as subarachnoid haemorrhage, confusional states, acute stroke, status epilepticus, meningeal neoplasms, demyelinating diseases and vasculitis [1].

CSF examination—LP should be preceded by imaging examination. Given the high cost of neuroimaging exploration, the American College of Emergency Physicians (ACEP), following a comprehensive review of the literature in 2002, makes the following recommendation (level C): ‘Adult headache patients with signs of intracranial hypertension (ICH), papillary oedema, absence of venous pulsations on ophthalmoscopic examination, altered mental status or focal neurological signs should be investigated initially by computer tomography (CT)’. The absence of signs of ICH allows a puncture without CT [2].

LP is recommended when suspected:

• Meningitis/encephalitis, subarachnoid haemorrhage (SAH), lymphomatosis, meningeal carcinomatosis,

• CSF pressure abnormalities that may be responsible for headache:

  • Pressure drop, below 90 mm H2O, post-traumatic brain injury (TBI) or LP,

  • increased pressure, above 200-250 mm H2O in idiopathic ICH, intracranial expansive processes, infectious processes, or intracranial haemorrhage.

• Suspicion of SAH even with normal CT requires LP with CSF examination. Fluid obtained by LP certifies the diagnosis of SAH if, being haemorrhagic, it shows a xanthochromic supernatant.

• In blood dyscrasias, LP may be performed when the platelet count is above 50,000/mmc [2].

2. Contents

2.1 Clinical signs and symptoms suggestive of CSF analysis are

2.1.1 Headache

Headaches are among the most common complaints of patients presenting to primary care and neurology and account for approximately 2% of all emergency department visits [3].

Because of its myriad potential causes, from benign to catastrophic, headache presents the clinician with a number of diagnostic and therapeutic challenges [3].

The results of the history and physical examination dictate appropriate diagnostic evaluations [3].

Faced with a patient with headache, the major clinical responsibility is to rule out structural or dynamic causes. Any expansive brain lesion can cause headache [1].

Headache characteristics of ICH. The location of the pain is not specific, although when a progressive headache begins at the back of the neck, herniation of the cerebellar tonsils is imminent. Headache is:

1. more pronounced in the morning;

2. aggravated by sitting or standing and improved by clinostatism;

3. aggravated by coughing, sneezing and vomiting;

4. relieved by aspirin or paracetamol in the early stages (in contrast to psychogenic headache);

5. associated with vomiting and eventually with papillary oedema and progressive focal signs. In the stuporous stage with hemiplegia and a mydriatic pupil (Hutchinson’s) the diagnosis is late [1].

Sudden-onset headache occurs in TBI, spontaneous intracranial haemorrhages, hydrocephalus or meningeal irritation at any age, the elderly not being immune. The most common cause is acute meningeal irritation due to SAH or bacterial or viral (rarely fungal or malignant) meningitis. An abrupt onset with fever, headache and Kernig’s sign accompanies severe headache, vomiting and photophobia. CSF analysis is mandatory if an infection is considered but after ruling out a brain abscess, tumour or haematoma [1].

LP is mandatory in cases of possible SAH (when neuroimaging alone is 99% sensitive), infectious or eosinophilic meningoencephalitis or pseudotumor cerebri. CSF is analysed for cells, protein, glucose, culture, cytology or special tests when warranted. In cases of possible haemorrhage, CSF should be centrifuged to detect the presence of xanthochromia. Opening pressure is compensated for in any patient with headache which does LP [3].

2.1.2 Changes in mental state

CNS dysfunctions (either decreased functioning leading to obnubilation and eventually coma, or reverse—hyperactivity leading to delirium) may be due to a primary neurological condition or may be secondary to a medical condition. Determining the patient’s initial (baseline) mental status is crucial for identifying mild mental status disorders. More severe disturbances have more obvious presentations, but in all cases, from mild to severe, the clinical history of onset, progression and coexisting features are essential to identify the underlying cause [3].

Consciousness is the ability of the individual in a vigilant state to realise his or her own existence and that of the environment and to have adequate perception and responsiveness. Consciousness is an active process with multiple components, including attention, memory, motivation, abstract thinking and the performance of actions with different purposes [4].

In the physiology of the nervous system, two important properties of consciousness are described: (1) the level of consciousness, which quantitatively estimates perception, reactivity and alertness status, and (2) the content of consciousness, which qualitatively estimates perception and reactivity [4].

Pathological alterations in consciousness may result from damage to the nervous system or metabolic disturbances caused by systemic diseases. Consciousness is clinically assessed by testing the patient’s ability to respond to sensory stimuli. If this ability is impaired, there is an altered state of consciousness. Impairment can occur in the sense of impaired level of consciousness, content of consciousness or both [4].

Confusion affects the content of consciousness, and the patient thus has a disorder of attention and concentration, temporal-spatial orientation, memory and/or perception (does not recognise certain places, people, names, etc.). The confused patient is not coherent in thought and actions. Confusion is a syndrome and not a disease, and the aetiology of confusional syndromes is varied [4].

Neurological focal lesions can also cause a confusional syndrome. Examples are subdural haematomas, strokes, brain tumours, encephalitis and meningitis. Delirium is a specific confusional syndrome with varied cognitive and behavioural symptoms, with acute onset (onset within hours or days), characterised by disturbance of attention and perception, with visual hallucinations, agitation, vegetative disturbances and fluctuations in symptom intensity (worsening in the evening) [4].

Akinetic mutism occurs through bifrontal lesions or hydrocephalus and is characterised by the preservation of consciousness, with the inability to initiate voluntary movements and verbal expression, even under nociceptive stimulation. It should be distinguished not only from comatose states but also from psychogenic conditions, periodic paralysis, Guillain-Barré syndrome (GBS) or myasthenia gravis [4].

In the clinical assessment of coma, the practitioner needs to determine whether or not neurological signs of outbreak are present and whether the patient has meningeal syndrome. In this way, he obtains important information about the neurological or toxic-metabolic aetiology of the coma [4].

LP is indicated in all cases where meningitis is suspected and in all patients with suspected SAH in whom CT screening is negative [3].

2.1.3 Fever

Symptoms of meningitis include fever along with other specific symptoms.

2.1.4 Sensitivity to light (photophobia)

Light sensitivity (photophobia) occurs in both meningitis and SAH symptoms.

2.1.5 Seizures

Seizures are quite common and the causes are extremely diverse (multiple sclerosis, meningitis, SAH, etc.).

Advances in the understanding of seizure types and the use of new types of antiepileptic drugs (AEDs) have increased the ability of the emergency physician to accurately diagnose the cause of a patient’s seizures and to rationally and systematically treat both the underlying abnormality and the seizures it produces [3].

LP is done when a CNS infection is suspected, and there are no signs of increased intracranial pressure. The pressure at the opening is recorded, and CSF is collected for blood counts including leukocyte count (WBC), protein, glucose, Gram stain, acid-fast bacilli (Ziehl-Neelsen), cryptococcal antigen, Venereal Disease Research Laboratory (VDRL) test, bacterial culture and counterimmunoelectrophoresis or agglutination reactions for bacterial antigens. It is important to note that CSF tests may indicate pleocytosis after a single simple or complex partial seizure, a generalised tonic-clonic seizure or status epilepticus (SE). If a CNS infection is suspected, its treatment is not delayed on the assumption that pleocytosis is due to seizures alone [3].

2.1.6 Gait disorders

Gait disorders are a common finding in the emergency department and usually reflect a nervous system disorder. Orthostasis and gait are unique to each person and reflect gender, age, body habitus, mood and even culture. The purpose of the assessment is to determine the part(s) of the nervous system involved in the type of gait observed [3].

Normal pressure hydrocephalus, a CSF circulation disorder, typically begins with progressive gait difficulties, which are the most marked symptom of the disease [5].

Steps are very small and hesitant, and the feet tend to be “drawn”, as if “magnetised”, to the floor. Patients may be slightly off-balance towards the back [3].

2.1.7 Dizziness

The word dizziness is a non-specific term used by both patients and medical professionals to describe a disturbance in sensation of well-being; dizziness is usually perceived as altered spatial orientation. Vertigo is defined as the illusion of movement of one’s own body or surroundings. Dizziness or vertigo can be the result of numerous disorders of the complex human balance system. Despite the inherent complexity, the assessment of dizziness or vertigo in the emergency department can be simplified by adopting a systematic approach to the history, somatic examination and laboratory investigations. A useful diagnostic method is to determine whether the patient’s symptoms are due to disturbance of the vestibular or non-vestibular systems [3].

The central causes of these complaints are generally cerebrovascular disorders, infections (meningitis and encephalitis) and demyelinating diseases.

Traumatised patients with suspected stroke or meningitis will undergo the necessary examinations: CT, MRI or CSF examination, with as little mobilisation as possible and under antiemetic-antivertigo medication. These investigations may be postponed in other situations such as multiple sclerosis, relapsing vertigo without alarming neuronal signs, etc. [6].

2.1.8 Decreased muscle strength (“muscle weakness”)

Decreased muscle strength (muscle weakness or muscle strength deficiency) is a condition where the muscles can no longer exert normal force. The inability to perform a specific normal activity suggests decreased muscle strength, which can easily be differentiated from decreased energy or endurance [3].

Decreased muscle strength implies an inability to perform usual activities due to decreased muscle, nerve or upper motor neuron function, not decreased energy or endurance (stamina) [3].

Acute inflammatory demyelinating polyneuropathy, also known as GBS, is the most common nerve root injury to reach emergency departments. The criteria required for the clinical diagnosis of GBS are decreased muscle strength with fairly symmetrical distribution and hypo- or areflexia [3].

In the initial phase, in the presence of numbness and decreased muscle strength with ascending character, a high index of suspicion of GBS is necessary, as auxiliary investigations may not be of any help. Normal CSF protein levels in the initial phase or the finding of numerous lymphocytes do not exclude the diagnosis of GBS. Towards the end of the first week of illness, CSF examination usually shows normal CSF pressure and elevated protein but without leucocytosis, which is called albumin-cytological dissociation [3].

2.2 Representative clinical aspects for which CSF analysis is essential

CSF examination is an essential tool in the diagnosis of certain neurological diseases. It aims to establish appearance, chemical and cytological composition and CSF pressure.

• the appearance of the fluid (under normal conditions, the fluid is clear and perfectly transparent);

• cytological study (normal CSF contains 1-5 figurative elements/mm³, mainly lymphocytes);

• chemical composition study (normal cerebrospinal fluid proteins are 20-35 mg/dl; normal glycoprotein is 60 mg/dl);

• CSF pressure (normal CSF pressure is 65-195 mmH2O or 15 mm Hg).

2.2.1 Benign intracranial hypertension

Synonyms—Pseudotumor cerebri, idiopathic intracranial hypertension.

Definition—Benign intracranial hypertension is a syndrome of increased intracranial pressure that occurs in the absence of an intracranial tumour or hydrocephalus. Synonyms pseudotumor cerebri or idiopathic intracranial hypertension is preferred because the course of this morbid entity is not always benign. Although rarely life-threatening, increased intracranial pressure may result in permanent loss of vision due to optic nerve damage [1].

Pathophysiology

1. The underlying cause of the elevated intracranial pressure is not known, but it is thought to result from a mismatch between spinal fluid production and absorption or increased resistance to absorption or functional lateral venous sinus obstruction.

2. Traction from swelling or pressure of dilated venous sinuses on pain-sensitive, large cerebral vessels may produce headache.

3. Obesity, anaemia and use of substances such as oestrogen-containing contraceptives, vitamin A or tetracycline may affect spinal fluid balance and provoke the condition [7].

Signs and symptoms—Almost all patients present with generalised headache, daily or almost daily, of fluctuating intensity, sometimes associated with nausea. They may have transient visual impairment, diplopia (due to dysfunction of cranial nerve pair VI) and intracranial, pulsatile tinnitus. Vision loss begins peripherally and may not be noticed by the patient until late in the course of the disease. The main danger is permanent loss of vision [8].

Bilateral papilledema is almost always present. There are a few patients who are asymptomatic but have palpebral oedema discovered on routine ophthalmoscopic examination. Neurological examination may reveal partial cranial VI nerve paresis which otherwise goes unnoticed [8].

The diagnosis is clinically suspected and is confirmed by brain imaging tests (preferably MRI with magnetic resonance venography) and by LP in which increased pressure with normal CSF composition occurs [8].

Treatment

1. Medical therapy is used for patients without visual loss and includes

   1. A medication, usually acetazolamide, to lower intracranial pressure

   2. Weight loss, if appropriate

   3. Steroids are used by some clinicians if visual loss is present.

2. Surgical therapy is reserved for patients with visual loss or poor response to medical therapy and includes

   1. Cerebrospinal fluid (CSF) shunting procedures, especially lumboperitoneal shunt

   2. Optic nerve sheath fenestration, which some believe to be the best procedure to preserve vision

   3. Stenting of functional lateral venous sinus obstruction is under study [7].

2.2.2 Intracranial hypertension (ICH)

The intact skull and spine, together with the relatively inelastic dura, make up a rigid structure (like a container), so increasing the volume of any of its components—brain, blood or CSF—will increase intracranial pressure [5].

ICH is caused by many things: intracranial expansive processes, stroke, infections (meningitis, encephalitis), cerebral oedema, hydrocephalus, CSF accumulation in the cranial cavity and hypertension in the cerebral vessels.

Clinical manifestations of ICH in children and adults are headache, nausea and vomiting, drowsiness, eye paresis and papillary oedema [5].

2.2.3 Intracranial hypotension

Pathogenic mechanisms involved in the occurrence of the condition:

• CSF loss;

• reduced CSF production.

Clinical picture: migraine in orthostatic position (as postpunctional migraine), mild meningismus; rare: cranial nerve deficits (abducens nerve), nausea, vomiting, unsystematised vertigo, tinnitus (possibly due to intralabyrinthine pressure change) [9].

Additional diagnosis

• CSF examination

• CSF pressure < 6 cm H2O (similar to “blind puncture”, air is sucked into the subarachnoid space), CSF must be aspirated with syringe

• slight pleocytosis (lymphocytic) (possible by meningeal irritation), slight protein increase (possible by reduced CSF flow into lumbar subarachnoid space)

• cytology: differential diagnosis with neoplastic meningitis [9]

2.2.4 Hydrocephalus

The term “hydrocephalus” means “water in the head” in Greek.

Hydrocephalus can be due to broadly two mechanisms that can be grouped into two categories: (1) excessive CSF production and (2) decreased CSF reabsorption, which may be caused by a mechanical obstruction located anywhere in the ventricular and cisternal CSF pathways, or by a reabsorption defect itself [10].

In adults, the most common causes are degenerative brain diseases, tumours, strokes, infections and haemorrhages.

Normal pressure hydrocephalus (NPH) is a syndrome that occurs in the elderly and consists of dementia, gait disorder and urinary incontinence associated with ventriculomegaly and normal CSF pressure [3].

Gait disturbance is usually the first symptom of NPH, an important clinical element that differentiates NPH from other dementias. Also, the severity of gait disturbance is the best predictor of clinical improvement following ventriculoperitoneal shunting. Gait abnormalities are characterised by the widened base of support, hesitant gait onset (apraxia) and frequent falls [3].

LP, rarely indicated by the emergency department in the absence of suspicion of other pathological processes, shows CSF pressure values of 80 to 150 mm water column (H₂O) and normal CSF analysis. Some patients with NPH have temporary improvements in gait disturbance and cognitive functioning after extraction of 20-50 ml of CSF (spinal tap test) [3].

2.2.5 Subarachnoid haemorrhage (SAH)

SAH is a non-traumatic cerebral haemorrhage in which blood extravasates into the meningeal spaces at the subarachnoid level (between the arachnoid and pia mater). The most common cause of SAH is ruptured aneurysms in the pial vessels (more than 80% of cases). Rarer causes are cerebral arteriovenous malformations (AVMs), cavernous malformations, arterial hypertension (AH), arterial dissections, coagulopathies, mycotic aneurysms, brain tumours, dural fistulas [4].

Core Features

1. Thunderclap headache. ‘Worst headache of my life’. Sudden headache that is maximal in intensity at onset is highly suspicious for (SAH) but more gradual headaches are also compatible with this diagnosis. Some patients may have a history of thunderclap headache prior to SAH (‘sentinel bleed’).

2. Altered level of consciousness.The level of arousal at presentation correlates with prognosis. A clear sensorium predicts better outcomes; coma portends the worst prognosis.

3. Non-contrast head CT shows blood in the subarachnoid space. The sensitivity of non-contrast head CT for SAH within hours of bleeding is very high when read by an experienced neuroradiologist. As blood resolves, sensitivity decreases, and only 50% of patients will have subarachnoid blood on non-contrast head CT 1 week following the bleed.

4. Blood and blood products (bilirubin) in the cerebrospinal fluid (CSF). The absence of red blood cells (RBCs) in the CSF at the time of presentation excludes the diagnosis of SAH. Xanthochromia, a yellow tinge of the CSF due to the presence of bilirubin, may not be observable at onset as it develops within 12 hours of bleeding and dissipates within 3 weeks.

5. Cerebral aneurysm visualised on CT or MR angiogram. Conventional catheter cerebral angiography is traditionally considered the gold standard for diagnosis of cerebral aneurysms, but the non-invasive CTA can detect aneurysms as small as 2 mm in diameter and is usually adequate for ruling out aneurysms [11].

2.2.6 Central nervous system (CNS) infections

Infectious diseases affecting the CNS are numerous and heterogeneous, in both pathogenic mechanisms and clinical manifestations. All known types of infectious agents (bacteria, viruses, fungi, parasites, prions) can affect the nervous system, either directly or by triggering a pathological immune response with a cross-mechanism. Certain neuroinfections, such as those with Treponema pallidum, Borrelia burgdorferi, Koch’s bacillus or human immunodeficiency virus, can take many forms and cause almost any neurological sign [4].

From the beginning, it should be noted that the diagnosis of the vast majority of neuroinfections requires LP, as CSF is the only CNS biological sample that is relatively easy to access [4].

Clinical manifestations of CNS infections are fever, headache, altered mental status—lethargy and confusion, seizures, neurological signs of outbreak and headache [12].

Depending on the location of the infection and clinical manifestations will be grouped into several major syndromes: encephalitic syndrome, meningeal syndrome and myelitis syndrome [4].

Acute bacterial meningitis

Acute bacterial meningitis is fulminant, with fatal pyogenic infection starting in the meninges. Symptoms include headache, fever and a stiff neck. In the absence of prompt treatment, it progresses to obnubilation and coma. Diagnosis is made by CSF examination [8].

LP with CSF analysis is the essential diagnostic manoeuvre in bacterial meningitis. Characteristic CSF changes are increased pressure, turbulent or purulent macroscopic appearance, pleocytosis (1000-10,000 leukocytes/mm³), 90% of which are polymorphonuclears, hyperproteinaemia (100-500 mg/dl), low glycoproteinaemia (below 40 mg/dl). In addition, Gram staining of the CSF sediment is performed, which in most cases identifies germs. In addition to blood cultures, it is useful also to seed CSF on culture medium and perform antibiogram. Enzyme-linked immunosorbent assay (ELISA), polymerase chain reaction (PCR) or immunoelectrophoresis are required for aetiological diagnosis of infection [4].

Brain abscess

Brain abscess is an infection located in the brain parenchyma, following spread from a nearby septic focus (otomastoiditis, sinusitis—this is why it frequently occurs in the temporal lobe), remote seeding (in endocarditis, pneumonia, patients with cardiac malformations, even dental infections) or by direct inoculation of germs (TCC or neurosurgical intervention) [4].

It manifests clinically as a space replacement process (headache and nausea/vomiting) associated with febrile syndrome, altered consciousness and focal neurological signs, depending on the location [4].

CSF culture-based inoculation can often identify the pathogen and antibiotics can guide treatment [4].

Subdural empyema

Subdural empyema is a collection of pus located between the dura mater and the arachnoid. Symptoms include fever, lethargy, focal neurological deficits and seizures [8].

Brain CT or preferably brain MRI (which better shows interhemispheric and hemispheric convexity collections) and CSF with high protein numbers, modest pleocytosis (50 leukocytes/mm3), and low glucose clear the diagnosis [4].

Epidural abscess

Epidural (“peridural”) abscess is a suppurative collection that may be located in the skull or spinal cord between the dura mater and the inner bony plate of the skull or vertebral arch. Seeding often occurs directly, during neurosurgical manoeuvres and trauma, from the vicinity (paranasal sinuses, middle ear, orbit) and less often by haematogenous seeding [4].

Patients with cerebral epidural abscess frequently associate meningitis, brain abscess and subdural empyema. The germs frequently involved are streptococci and staphylococci. CT with contrast or possibly MRI with contrast detects the collection, CSF may be normal if the abscess has not penetrated the subdural or subarachnoid space [4].

Tuberculous meningitis

The incidence of tuberculosis (TB) is on the rise due to an increase in the number of HIV-infected people, homeless people and immigrants from developing countries [3].

In conditions of clinical suspicion for diagnosis, an LP should be performed, preceded by fundoscopic examination, which may identify papillary oedema (common in tuberculous meningitis), optic atrophy or even retinal tuberculosis [4].

CSF typically shows a much-increased proteinaemia (the most important of all meningitis), up to 1000 mg/dl, with fibrin deposits and the sign of the present veil (heating the CSF tube with flame leads to the precipitation of excess proteins and their appearance as a whitish “veil”), low glucose, pleocytosis 100–500 leukocytes/mm³, of which more than 50% neutrophils. Pleocytosis is usually absent in HIV-positive and immunosuppressed patients. CSF pressure is usually increased. However, the macroscopic appearance is clear, which has led to the classic classification of tuberculous meningitis as “aseptic” meningitis (with clear, non-purulent CSF; aseptic meningitis also includes viral meningitis, carcinomatous meningitis, Lyme meningitis and meningitis from vasculitis and granulomatous diseases). CSF is generally paucibacillary, Koch’s bacilli being difficult to detect. Cultures are made by seeding on a special medium (Lowenstein) and then Ziehl-Nielson staining, but slightly more than half of cases can be etiologically diagnosed in this way. The PCR method is much more sensitive but more expensive [4].

Neurosyphilis

Syphilis is a sexually transmitted disease, and the pathogen responsible is Treponema pallidum, a Gram-negative spirochete (the spirochete family also includes the Borrelia and Leptospira genera) [4].

In the CNS, the infection causes chronic inflammation of the meninges, which over time can be complicated by parenchymal lesions [4].

More specific laboratory tests, such as the CSF Venereal Disease Laboratory (VDRL) test or the fluorescence treponemal antibody-antibody absorption test (FTA-ABS), combined with non-specific parameters (CSF pleocytosis greater than nine leukocytes per microscopic visual field of high magnitude, elevated CSF proteins and low glucose levels) are needed for accurate diagnosis of present or antecedent neurosyphilis in the context of the history and physical examination. Except in cases where CSF is contaminated with seropositive blood during lumbar puncture, positive VDRL reaction in CSF indicates previous or current neurosyphilis [3].

Neuroborreliosis

Borreliosis (Lyme disease—borreliosis was named Lyme disease because it was first described in the town of Old Lyme in Connecticut, USA, in 1975) recognises the spirochete Borrelia burgdorferi as the infectious agent, which is transmitted to humans through the bite of a tick (Ixodes ricinus) [4].

Diagnosis is based on the clinical picture, the presence of lymphocytic meningitis and serological confirmation of infection in serum and CSF. The first method used is usually ELISA (enzyme-linked immunosorbent assay), and in the case of a high titre of anti-Borrelia antibodies, Western blot (qualitative and semi-quantitative method of protein identification based on immunological principles) or PCR (polymerase chain reaction) is used for confirmation [4].

Encephalitis

Encephalitis is inflammation of the brain parenchyma due to direct viral invasion or hypersensitivity triggered by a virus or other foreign protein. Encephalomyelitis is the same process but involves the brain and spinal cord. These conditions can be caused by a variety of viruses. Symptoms consist of fever, headache and altered consciousness, often associated with seizures or focal neurological deficits. Diagnosis requires CSF analysis and neuroimaging investigations [8].

The diagnosis of encephalitis is suspected in patients with unexplained alterations in consciousness. If encephalitis is present, CSF analysis shows lymphocytic pleocytosis, normal glucose, slightly increased proteinaemia and absence of pathogens on culture and Gram stain (similar appearance to aseptic meningitis); CSF changes may occur 8-24 hours after the onset of symptoms. In case of haemorrhagic necrosis, CSF will show a lot of red blood cells and few neutrophils, increasing proteinuria and glycoradiation moderately decreasing. PCR analysis in CSF to identify herpes virus is sensitive and specific, but obtaining results may take time. Viral CSF cultures may show growth of enterovirus but less of other viruses. CSF and blood tests in both the acute and convalescent phases should be spaced a few weeks apart as they may show an increase in viral titre specific to certain viral infections [8].

Neurocysticercosis

Neurocysticercosis is the most common brain parasitosis and occurs following ingestion of pork infested with Taenia solium eggs. When they occur, the clinical manifestations consist of epileptic seizures, generalised or partial, migraine-type headache and behavioural disorders (Garg, 1988) [4].

Diagnosis involves evidence of cysticerci and perilesional oedema by brain CT or MRI (round, small, hypodense images on CT and hypointense in T1 sequence on MRI, possibly with calcifications), CSF with mononuclear pleocytosis, hyperproteinaemia, normal glucose, elevated IgG and sometimes oligoclonal bands, leucocytosis, with eosinophilia and ELISA with elevated CSF antibody titres [4].

Creutzfeldt-Jakob disease

Creutzfeldt-Jacob disease is a sporadic or familial prion disease. Bovine spongiform encephalopathy (mad cow disease) is a variant of the disease. Symptoms include dementia, myoclonus and other neurological deficits, with death occurring within 1-2 years [8].

CSF is biochemically and cellularly normal but contains elevated levels of 14-3-3 protein (assay has sensitivity and specificity over 90%) [4].

2.2.7 Demyelinating diseases

Multiple sclerosis

Multiple sclerosis (MS) is the most common form of demyelinating disease of the nervous system, with an autoimmune mechanism—i.e. abnormal production of antibodies directed against the destruction of the body’s own tissues/cells [12].

MS is characterised by areas of demyelination, spread throughout the brain and spinal cord. Common symptoms of MS are visual and oculomotor abnormalities, paraesthesia, muscle weakness, spasticity, urinary dysfunction and mild cognitive impairment [8].

CSF examination is altered in over 90% of patients. Moderate monocytic pleocytosis (dozens of cells/mm³) occurs mostly at onset and during episodes, corresponding to an exacerbation of the inflammatory process. In about half of patients, proteinaemia is above normal limits. The appearance of oligoclonal bands in the CSF (expression of immunoglobulins synthesised in the nervous system) is a test with high sensitivity (more than 90% of patients) but low specificity. In the same situation is the immunoglobulin index, which is calculated according to the formula: (CSF IgG/serum IgG): (CSF albumin/serum albumin), whose value greater than 1.7 is suggestive of diagnosis (normal value is around 1) [4].

2.2.8 Peripheral neuropathies

Guillain-Barré syndrome (GBS)

GBS (Acute idiopathic polyneuritis, Landry’s palsy, acute inflammatory demyelinating polyneuropathy) is a rapidly progressive inflammatory polyneuropathy characterised by muscle weakness and mild loss of distal sensation. The cause appears to be autoimmune. Diagnosis is clinical and treatment consists of plasmapheresis, administration of gamma globulin and, in severe cases, mechanical ventilation [8].

GBS can occur at any age. About 5-7 days after the onset of motor deficit, PL shows typical (pathognomonic) CSF biochemical changes: increased proteinaemia without pleocytosis (albumin-cytokine dissociation) [4].

3. Conclusions

Therefore, in addition to clinical aspects, CSF analysis is extremely useful in the diagnosis of certain neurological disorders.

Conflict of interest

The author declare no conflict of interest.

Abbreviations

CSF	cerebrospinal fluid
LP	lumbar puncture
CNS	central nervous system
ICH	intracranial hypertension
CT	computer tomography
SAH	subarachnoid haemorrhage
TBI	traumatic brain injury
GBS	Guillain-Barré syndrome
AEDS	antiepileptic drugs
SE	status epilepticus
NPH	normal pressure hydrocephalus
CNS	central nervous system
MS	multiple sclerosis