1. mononeuritis multiplex:
is characterised by lesions of multiple nerve roots, peripheral nerves or cranial nerves. It is due either to involvement of the vasa nervorum or to malignant infiltration of the nerves. The clinical expression of a very widespread multifocal neuropathy may become confluent so that the clinical picture eventually resembles a polyneuropathy. In this case neurophysiology may be required to identify the multifocal nature of the problem. Investigation of patients with an acute multifocal neuropathy should be urgent since vasculitis is a common cause, either as part of a systemic disease or isolated to the nerves.

2. Causes :
1- diabetes mellitus or impaired glucose tolerance.
2-vasulitis:RA,SLE,polyarteritis nodosa etc….
3-sarcoidosis.
4-amyloidosis.
5-infection:lyme disease .HIV,HBV,HCV ,leprosy etc…..
6-paraneoplastic.
7-sjogren syndrome.
Investigation and treatment :
Polyneuropathy:
According to the cause.
is a generalised pathological process occurring in the longest peripheral nerves first, affecting the distal lower limbs before the upper limbs, with sensory symptoms and signs of an ascending 'glove and stocking' distribution.

3. Guillain-Barré syndrome(acute inflammatory polyneuropathy):
A syndrome of acute paralysis develops , 1-4 weeks after respiratory infection or diarrhoea (particularly Campylobacter). Acute inflammatory polyneuropathy is most commonly demyelinating (acute inflammatory demyelinating neuropathy, AIDP). Axonal variants, either motor (acute motor axonal neuropathy, AMAN) or sensorimotor (acute motor and sensory axonal neuropathy, AMSAN), are more common in China and Japan.
There is a predominantly cell-mediated inflammatory response directed at the myelin protein of spinal roots, peripheral and extra-axial cranial nerves, possibly triggered by molecular mimicry between epitopes found in the cell walls of some microorganisms and gangliosides in the Schwann cell and axonal membranes. The resulting release of inflammatory cytokines blocks nerve conduction and is followed by a complement-mediated destruction of the myelin sheath and the associated axon.

4. Clinical features:
Distal paraesthesia and limb pains (often severe) precede a rapidly ascending muscle weakness, from lower to upper limbs, more marked proximally than distally. Facial and bulbar weakness commonly develops, and respiratory weakness requiring ventilatory support occurs in 20% of cases. In most patients, weakness progresses for 1-3 weeks, but rapid deterioration to respiratory failure can develop within hours.
On examination there is diffuse weakness with widespread loss of reflexes. An unusual axonal variant described by Miller Fisher comprises the triad of ophthalmoplegia, ataxia and areflexia. Overall, 80% of patients recover completely within 3-6 months, 4% die, and the remainder suffer residual neurological disability which can be severe.
Adverse prognostic features include:
1- older age.
2- rapid deterioration to ventilation .
3- evidence of axonal loss on EMG.

5. Investigations:
The CSF protein is elevated at some stage of the illness but may be normal in the first 10 days. There is usually no rise in CSF cell number (a lymphocytosis of > 50 × 106 cells/L suggests an alternative diagnosis) and this is called cytoalbumino dissociation. Electrophysiological studies are often normal in the early stages but show typical changes after a week or so, with conduction block and multifocal motor slowing, sometimes most evident proximally as delayed F-wave.
Investigation to identify an underlying cause, such as cytomegalovirus, mycoplasma or Campylobacter, requires a chest X-ray, stool culture and appropriate immunological blood tests. Acute porphyria should be excluded by urinary porphyrin estimation, and serum lead should be measured if there are only motor signs.
Antibodies to the ganglioside GQ1b are found in the Miller Fisher variant.

6. Management:
During the phase of deterioration, regular monitoring of respiratory function (vital capacity and arterial blood gases) is required, as respiratory failure may develop with little warning and require ventilatory support. Ventilation may be needed if the vital capacity falls below 1 L, but intubation is more often required because of bulbar incompetence leading to aspiration. General management to protect the airway and prevent pressure sores and venous thrombosis is essential. Corticosteroid therapy has been shown by RCT to be ineffective.
Plasma exchange and intravenous immunoglobulin therapy shorten the duration of ventilation and improve prognosis, provided treatment is started within 14 days of the onset of symptoms , but there is no advantage in combining the two treatments.
The dose of IVig is 0.4mg/Kg/day for 5days infusion, whereas plasma exchange is given as 5-7 sessions with interval of 2-3 days between the sessions.

7. Chronic demyelinating polyneuropathy CIDP:
CIDP is an acquired, treatable, demyelinating PNS disease characterized by progressive or relapsing proximal and distal weakness of the limbs with sensory loss and/or cranial nerve involvement reaching a nadir in more than 8 weeks with absent or reduced reflexes in all limbs. Unlike GBS there are no known predisposing infections. The CIDP is either primary (idiopathic) or secondary to underlying diseaes , all the efforts are directed to identify these causes .
Causes:
1-diabetes mellites.
2-connective tissue diseases .
3-lymphoma.
4-alkohol.
5-inflammatory bowel diseases.
6-systemic malignancy.
7-HIV.
8-sarcoidosis and amyloidosis.
9-multiple myeloma.

8. Symptoms and signs
Patients with CIDP present with a progressive or relapsing limb weakness or numbness which may have an asymmetrical onset. Parasthesiae are common. Limb and back pain occurs but if prominent should stimulate a search for alternative causes especially vasculitis, lymphoma or infection. Autonomic and bladder or bowel involvement is distinctly unusual. The clinical signs mirror the presentation. Proximal and distal weakness with areflexia and a distal sensory loss are common. Wasting is not evident until late in untreated disease. Progression to respiratory involvement and need for ventilation occurs rarely. A careful general examination is crucial to identify systemic causes or contributing factors .

9. Investigations
1 -Nerve conduction studies: Clear demonstration of demyelination in at least two nerves is mandatory for a definite diagnosis of CIDP if no other supportive criteria are employed. Demyelinating features of reduced motor conduction velocity, prolonged distal motor latencies or proximal F-waves or conduction block or dispersion.Later in the condition axonal degeneration may supervene.
2- CSF. :The CSF protein is raised in 90% of cases. A CSF white cell count of >10 mm3 should prompt a search for alternative causes.
3- MRI.: Nerve root enlargement and/or enhancement with gadolinium is often seen. Most commonly imaged areas include the cervical and lumbosacral regions. MRI findings are now included in the supportive criteria for the diagnosis.

10. 4- Nerve biopsy. A diagnosis of CIDP does not always require a nerve biopsy as the clinical presentation, neurophysiology and other less invasive paraclinical investigations are usually sufficient to make a diagnosis. Although the sural nerve is the most commonly biopsied, a suitable nerve should be selected on the basis of symptoms and electrophysiological findings; only very rarely should an electrically ‘normal’ nerve be biopsied. Biopsies contain reduced numbers of myelinated nerve fibres with evidence of active demyelination or previous onion bulb formation .
5- Blood tests. :There are no diagnostic blood tests for CIDP. Full blood count, ESR, B12 and folate, urea and electrolytes, glucose, liver and thyroid function tests, immunoglobulins, protein electrophoresis and immunofixation and ANA should be requested as an initial screen to rule out other conditions.
6- Exclusion of other conditions. Exclusion of other causative or contributing conditions is essential.

11. Treatment of typical CIDP
The first line treatments for CIDP are either oral steroids (although various regimens are used, 1 mg/kg given for 2 months and then slowly tapered is common) or IVIG (0.4 g/kg for 5 days repeated at 4–6 weeks and then as necessary according to the response). Both steroids and IVIG have been shown to be better than placebo and there is no clear difference between IVIG and steroids. Steroids should be co-prescribed with a bisphosphonate to protect against bone loss, and gastric pharmacoprotection should be considered. IVIG is a blood product and patients should be made aware of and consented for the risks.
If IVIG or steroids are contraindicated or ineffectual then plasma exchange should be considered. Other immunosuppressants have been tried in CIDP but cyclophosphamide is the only one to have shown promise.

12. Outcome
CIDP is a chronic progressive or relapsing disease. About 80% of patients will respond to treatment. Where patients fail to respond to treatment an occult paraprotein should be sought annually. Over half (54%) of patients require assistance to walk or are bed-bound at some stage of their illness; 13% of patients require assistance to mobilize or are bed-bound at any one time. Over 50% require continuous treatment to maintain stability.
Hereditary polyneuropathy :
This type of chronic polyneuropathy is hereditary . Many inherited disorders cause demyelinating peripheral neuropathies and one of the best known is Charcot-Marie-Tooth disease (CMT). Here the neuropathy produces distal wasting ('inverted champagne bottle' or 'stork' legs), often with pes cavus, and a predominantly motor clinical involvement. In 70-80% the cause is duplication of the PMP-22 gene on chromosome 17 (autosomal dominant CMT type 1), but similar phenotypes are produced by mutations in other genes with differing modes of inheritance.